18 results on '"Hiroto Izumi"'
Search Results
2. Novel WNT10A variant in a Japanese case of nonsyndromic oligodontia
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Junya Adachi, Yoshihiko Aoki, Hiroto Izumi, Takeshi Nishiyama, Atsuo Nakayama, Masatoshi Sana, Kyoko Morimoto, Atsuo Kaetsu, Takamasa Shirozu, Eriko Osumi, Michiko Matsuoka, Eri Hayakawa, Nasel Maeda, Junichiro Machida, Toru Nagao, and Yoshihito Tokita
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Genetics ,Molecular Biology ,Biochemistry - Abstract
Congenital tooth agenesis is one of the most common anomalies in humans. Many genetic factors are involved in tooth development, including MSX1, PAX9, WNT10A, and LRP6. Thus, mutations in these genes can cause congenital tooth agenesis in humans. In this study, we identified a novel nonsense WNT10A variant, NM_025216.3(WNT10A_v001):c.1090A > T, which produces a C-terminal truncated gene product, p.(Lys364*), in a sporadic form of congenital tooth agenesis. The variant was not found in the healthy parents and thus was considered to cause congenital tooth agenesis in the case.
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- 2023
3. Delivery of therapeutic oligonucleotides targeting Dectin-1 using quantized complexes
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Kazuki Sumiya, Hiroto Izumi, Takuya Matsunaga, Motoko Tanaka, and Kazuo Sakurai
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Polymers and Plastics ,Materials Chemistry - Published
- 2022
4. YBX2 and cancer testis antigen 45 contribute to stemness, chemoresistance and a high degree of malignancy in human endometrial cancer
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Atsuo Itakura, Kouichi Tabu, Soshi Kusunoki, Tetsuya Taga, Kenzo Sonoda, Hiroto Izumi, Yumiko Matsumura, Izumi Suzuki, Kimitoshi Kohno, Kazuo Asanoma, Kiyoko Kato, Ichiro Onoyama, Satoru Takeda, Sachiko Yoshida, and Hiroshi Yagi
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0301 basic medicine ,Paclitaxel ,Science ,Population ,Biology ,Article ,03 medical and health sciences ,0302 clinical medicine ,Endometrial cancer ,Antigens, Neoplasm ,Cancer stem cell ,Cell Line, Tumor ,Gene expression ,medicine ,Humans ,education ,education.field_of_study ,Multidisciplinary ,Cancer stem cells ,RNA-Binding Proteins ,medicine.disease ,Endometrial Neoplasms ,Gene Expression Regulation, Neoplastic ,030104 developmental biology ,Drug Resistance, Neoplasm ,Cell culture ,030220 oncology & carcinogenesis ,Cancer cell ,Neoplastic Stem Cells ,Cancer research ,Medicine ,Cancer/testis antigens ,Female ,Stem cell - Abstract
Y-box binding protein 2 (YBX2) has been associated with the properties of both germ cells and cancer cells. We hypothesized that YBX2 might contribute to the characteristics of cancer stem cells (CSCs). In this study, we clarified the function of YBX2 in endometrial cancer stem cells. We established a human YBX2-expressing Ishikawa (IK) cell line (IK-YBX2 cells). We analyzed gene expression associated with stemness and isolated SP cells from IK-YBX2 cells. The SP population of IK-YBX2 cells, the expression of ALDH1 and serial sphere-forming capacity were associated with levels of YBX2 expression. IK-YBX2 cells were resistant to anti-cancer drugs. In gene expression analysis, a gene for cancer testis antigen, CT45, was generally overexpressed in IK-YBX2 cells. YBX2-mediated CT45 expression was associated with increased levels of self-renewal capacity and paclitaxel resistance. The level of CT45 expression was enhanced in high-grade and/or advanced stages of human endometrial cancer tissues. We conclude that expression of YBX2 is essential for the stem cell-like phenotype. CT45 contributes to stemness associated with YBX2 and might be related to the progression of endometrial cancer.
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- 2021
5. The overexpression of peroxiredoxin-4 affects the progression of idiopathic pulmonary fibrosis
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Takashi Kido, Hirotsugu Noguchi, Sohsuke Yamada, Keishi Oda, Tetsuya Hanaka, Ke-Yong Wang, Hiroshi Mukae, Hiroshi Ishimoto, Hiroto Izumi, Xin Guo, Aya Nawata, Shingo Noguchi, Kazuhiro Yatera, and Tsutomu Takaki
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Adult ,Male ,Pulmonary and Respiratory Medicine ,medicine.medical_specialty ,Exacerbation ,Idiopathic pulmonary fibrosis ,Bleomycin ,Peroxiredoxin 4 ,Gastroenterology ,Mice ,03 medical and health sciences ,chemistry.chemical_compound ,0302 clinical medicine ,Fibrosis ,Lactate dehydrogenase ,Internal medicine ,Pulmonary fibrosis ,medicine ,Animals ,Humans ,Aged ,Retrospective Studies ,030304 developmental biology ,lcsh:RC705-779 ,0303 health sciences ,Lung ,business.industry ,Surfactant protein D ,lcsh:Diseases of the respiratory system ,Peroxiredoxins ,Middle Aged ,respiratory system ,medicine.disease ,humanities ,respiratory tract diseases ,Disease Models, Animal ,Acute exacerbation ,medicine.anatomical_structure ,030228 respiratory system ,chemistry ,Disease Progression ,Female ,business ,Biomarkers ,Research Article - Abstract
Background Acute exacerbation of idiopathic pulmonary fibrosis (AE-IPF) is life-threatening. Several serum biomarkers, such as Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D), are clinically used for evaluating AE-IPF, but these biomarkers are not adequate for establishing an early and accurate diagnosis of AE-IPF. Recently, the protective roles of the members of the peroxiredoxin (PRDX) family have been reported in IPF; however, the role of PRDX4 in AE-IPF is unclear. Methods Serum levels of PRDX4 protein, KL-6, SP-D and lactate dehydrogenase (LDH) in 51 patients with stable IPF (S-IPF), 38 patients with AE-IPF and 15 healthy volunteers were retrospectively assessed using enzyme-linked immunosorbent assay. Moreover, as an animal model of pulmonary fibrosis, wild-type (WT) and PRDX4-transgenic (Tg) mice were intratracheally administered with bleomycin (BLM, 2 mg/kg), and fibrotic and inflammatory changes in lungs were evaluated 3 weeks after the intratracheal administration. Results Serum levels of PRDX4 protein, KL-6, SP-D and LDH in patients with S-IPF and AE-IPF were significantly higher than those in healthy volunteers, and those in AE-IPF patients were the highest among the three groups. Using receiver operating characteristic curves, area under the curve values of serum PRDX4 protein, KL-6, SP-D, and LDH for detecting AE-IPF were 0.873, 0.698, 0.675, and 0.906, respectively. BLM-treated Tg mice demonstrated aggravated histopathological findings and poor prognosis compared with BLM-treated WT mice. Moreover, PRDX4 expression was observed in alveolar macrophages and lung epithelial cells of BLM-treated Tg mice. Conclusions PRDX4 is associated with the aggravation of inflammatory changes and fibrosis in the pathogenesis of IPF, and serum PRDX4 may be useful in clinical practice of IPF patients.
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- 2019
6. Usefulness of myeloperoxidase as a biomarker for the ranking of pulmonary toxicity of nanomaterials
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Chinatsu Nishida, Shingo Noguchi, Hiroto Izumi, Takashi Marui, Takami Okada, Masaru Kubo, Ke-Yong Wang, Manabu Shimada, Takako Oyabu, Toshihiko Myojo, Yasuo Morimoto, Byeong-Woo Lee, Taisuke Tomonaga, Yukiko Yoshiura, and Kazuhiro Yatera
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Male ,0301 basic medicine ,Neutrophils ,Pulmonary toxicity ,Health, Toxicology and Mutagenesis ,lcsh:Industrial hygiene. Industrial welfare ,010501 environmental sciences ,Pharmacology ,Toxicology ,01 natural sciences ,03 medical and health sciences ,chemistry.chemical_compound ,lcsh:RA1190-1270 ,Lactate dehydrogenase ,Macrophages, Alveolar ,medicine ,Animals ,Lung ,Peroxidase ,lcsh:Toxicology. Poisons ,0105 earth and related environmental sciences ,Inhalation exposure ,Inhalation Exposure ,Myeloperoxidase ,Inhalation ,medicine.diagnostic_test ,biology ,Research ,Biomarker ,General Medicine ,Nanomaterial ,Rats, Inbred F344 ,Heme oxygenase ,030104 developmental biology ,Bronchoalveolar lavage ,chemistry ,Toxicity ,biology.protein ,Rat ,Nanoparticles ,Chemokines ,Bronchoalveolar Lavage Fluid ,Intratracheal instillation ,Biomarkers ,lcsh:HD7260-7780.8 - Abstract
Background In order to examine whether myeloperoxidase (MPO) can be a useful marker for evaluating the pulmonary toxicity of nanomaterials, we analyzed MPO protein in bronchoalveolar lavage fluid (BALF) samples obtained from previous examinations of a rat model. In those examinations we performed intratracheal instillation exposures (dose: 0.2–1.0 mg) and inhalation exposures (exposure concentration: 0.32–10.4 mg/m3) using 9 and 4 nanomaterials with different toxicities, respectively. Based on those previous studies, we set Nickel oxide nanoparticles (NiO), cerium dioxide nanoparticles (CeO2), multi wall carbon nanotubes with short or long length (MWCNT (S) and MWCNT (L)), and single wall carbon nanotube (SWCNT) as chemicals with high toxicity; and titanium dioxide nanoparticles (TiO2 (P90) and TiO2 (Rutile)), zinc oxide nanoparticles (ZnO), and toner with external additives including nanoparticles as chemicals with low toxicity. We measured the concentration of MPO in BALF samples from rats from 3 days to 6 months following a single intratracheal instillation, and from 3 days to 3 months after the end of inhalation exposure. Results Intratracheal instillation of high toxicity NiO, CeO2, MWCNT (S), MWCNT (L), and SWCNT persistently increased the concentration of MPO, and inhalation of NiO and CeO2 increased the MPO in BALF. By contrast, intratracheal instillation of low toxicity TiO2 (P90), TiO2 (Rutile), ZnO, and toner increased the concentration of MPO in BALF only transiently, and inhalation of TiO2 (Rutile) and ZnO induced almost no increase of the MPO. The concentration of MPO correlated with the number of total cells and neutrophils, the concentration of chemokines for neutrophils (cytokine-induced neutrophil chemoattractant (CINC)-1 and heme oxygenase (HO)-1), and the activity of released lactate dehydrogenase (LDH) in BALF. The results from the receiver operating characteristics (ROC) for the toxicity of chemicals by the concentration of MPO proteins in the intratracheal instillation and inhalation exposures showed that the largest areas under the curves (AUC) s in both examinations occurred at 1 month after exposure. Conclusion These data suggest that MPO can be a useful biomarker for the ranking of the pulmonary toxicity of nanomaterials, especially at 1 month after exposure, in both intratracheal instillation and inhalation exposure. Electronic supplementary material The online version of this article (10.1186/s12989-018-0277-x) contains supplementary material, which is available to authorized users.
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- 2018
7. WNT10A variants isolated from Japanese patients with congenital tooth agenesis
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Akio Shibata, Kazuo Shimozato, Hiroto Izumi, Yoshihito Tokita, Hitoshi Miyachi, Tadashi Tatematsu, Katsu Takahashi, Junichiro Machida, Atsuo Nakayama, and Hiroaki Goto
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0301 basic medicine ,business.industry ,Wnt signaling pathway ,030206 dentistry ,Bioinformatics ,Biochemistry ,Phenotype ,stomatognathic diseases ,03 medical and health sciences ,030104 developmental biology ,0302 clinical medicine ,stomatognathic system ,Data Report ,Genetics ,Medicine ,Tooth agenesis ,business ,Molecular Biology - Abstract
It has been reported that dozens of WNT10A variants are associated with human isolated tooth agenesis, however, little is known about the precise phenotypes. In 50 Japanese patients with severe congenital tooth agenesis, we identified 11 patients with WNT10A variants. Comparing phenotypes between the tooth agenesis patients carrying the wild-type and variants of WNT10A, we revealed that the development of lateral incisors is relatively susceptive to insufficiency of WNT/β-catenin signaling.
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- 2017
8. Polypeptide N-acetylgalactosaminyltransferase 6 expression in pancreatic cancer is an independent prognostic factor indicating better overall survival
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Ke-Yong Wang, Yasuyuki Sasaguri, Inenaga S, Hiroto Izumi, Toshihiro Imamura, Shohei Shimajiri, Kimitoshi Kohno, Li Z, Ying Wu, Sohsuke Yamada, and Nakano R
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Adult ,Male ,Oncology ,Cancer Research ,medicine.medical_specialty ,Pathology ,Pancreatic disease ,pancreatic cancer ,Polypeptide N-acetylgalactosaminyltransferase ,Biology ,Metastasis ,Cell Line, Tumor ,Internal medicine ,Pancreatic cancer ,parasitic diseases ,medicine ,metastasis ,Humans ,Clinical significance ,Molecular Diagnostics ,Pathological ,Aged ,Cancer ,Middle Aged ,Prognosis ,medicine.disease ,Immunohistochemistry ,Pancreatic Neoplasms ,carbohydrates (lipids) ,GalNAc-T6 ,N-Acetylgalactosaminyltransferases ,GalNAc-T3 ,Female ,lipids (amino acids, peptides, and proteins) - Abstract
Background: The family of polypeptide N-acetylgalactosaminyltransferases (GalNAc-Ts) is responsible for the altered glycosylation in cancer. The purpose of our study was to investigate the clinical significance of two isoforms, GalNAc-T6 and -T3, and their correlation with the prognosis of pancreatic cancer. Methods: Immunohistochemistry was used to analyse GalNAc-T6 and -T3 expressions in 70 clinicopathologically characterised pancreatic cancer cases. Results: Positive expressions of GalNAc-T6 and -T3 were immunohistochemically identified in 51% (36 of 70) and in 77% (54 of 70) of patients, respectively. A close relationship was noted between GalNAc-T6 positive expression and pathological well/moderate differentiated type (P=0.001), small tumour size (P=0.044), absence of vascular invasion (P=0.009), and low stage of the American Joint Committee on Cancer systems (P=0.043). The expression of GalNAc-T3 significantly correlated with good differentiation (P=0.001), but not with other clinicopathologic features. Furthermore, univariate and multivariate analyses revealed that GalNAc-T6 expression was an independent prognosis indicator for the disease, whereas GalNAc-T3 expression had no impact on clinical outcome, even though 33 of 36 GalNAc-T6-positive cases also had a positive expression of GalNAc-T3 (P=0.001, r=0.356). Conclusion: Both GalNAc-T6 and -T3 expressions correlated significantly with tumour differentiation, whereas only GalNAc-T6 expression predicted prognosis in pancreatic cancer.
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- 2011
9. Mina53, a novel c-Myc target gene, is frequently expressed in lung cancers and exerts oncogenic property in NIH/3T3 cells
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Toshimi Sato, Takashi Hisatomi, Akemi Sato, Eisaburo Sueoka, Masahiro Mitsuoka, Naoko Sueoka-Aragane, Toru Sakuragi, Makoto Tsuneoka, Shinichiro Hayashi, Hiroto Izumi, and Kazutoshi Komiya
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Male ,Cancer Research ,Lung Neoplasms ,medicine.medical_treatment ,Transplantation, Heterologous ,Cell ,Clone (cell biology) ,Mice, Nude ,Adenocarcinoma ,Biology ,medicine.disease_cause ,Dioxygenases ,Proto-Oncogene Proteins c-myc ,Mice ,Gene expression ,medicine ,Animals ,Humans ,Lung cancer ,Cells, Cultured ,Neoplasm Staging ,Oligonucleotide Array Sequence Analysis ,Histone Demethylases ,Microarray analysis techniques ,Gene Expression Profiling ,Nuclear Proteins ,Cancer ,General Medicine ,medicine.disease ,Gene Expression Regulation, Neoplastic ,Cell Transformation, Neoplastic ,Cytokine ,medicine.anatomical_structure ,Oncology ,NIH 3T3 Cells ,Cancer research ,Female ,Carcinogenesis - Abstract
Mina53, whose expression is directly induced by c-Myc, is overexpressed in various cancers and plays an important role in cell growth. To clarify the involvement of Mina53 in lung cancers, we investigated its expression in human lung cancer tissues as well as in various lung cancer cell lines. Mina53 expression was determined by real-time RT-PCR, western blotting, and immunohistochemistry using lung cancer cell lines, normal human bronchial epithelial cells, and lung cancer tissues. Biological effects of Mina53 were evaluated by soft agar colony formation assay and tumorigenicity in nude mice using Mina53-transfected NIH/3T3 cells. cDNA microarray analysis was performed to determine the gene alteration by Mina53 and confirmation was made using real-time RT-PCR with mina53 expression plasmid or mina53 shRNA-transfected NIH/3T3 cells. We observed that 62% of patients evidenced overexpression of Mina53 from the early clinical stages of lung cancer. Differences according to gender, smoking status, or histologic type were not statistically significant. Forced expression of Mina53 in NIH/3T3 cells induced cell transformation, and mina53-transfected NIH/3T3 clones produced tumors in nude mice, demonstrating that Mina53 has oncogenic potential. cDNA microarray revealed that 254 genes had altered expression in a mina53-transfected NIH/3T3 clone. Mina53 regulates several genes related to cell adhesion and metabolism, which have also been reported to be regulated by c-Myc. Genes regulated by Mina53, but not by c-Myc included cytokine/growth factor related genes such as EGFR, IL-6, and HGF. Our results suggest that Mina53 plays an important role in carcinogenesis and may be a target for cancer prevention.
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- 2009
10. ZNF143 interacts with p73 and is involved in cisplatin resistance through the transcriptional regulation of DNA repair genes
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Kazuto Nishio, Takeshi Uchiumi, Tokuzo Arao, Kimitoshi Kohno, Hideaki Suzuki, Hiroto Izumi, and Tetsuro Wakasugi
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Cancer Research ,DNA Repair ,Transcription, Genetic ,Tumor suppressor gene ,DNA repair ,Antineoplastic Agents ,Biology ,medicine.disease_cause ,TRNA transcription ,Cell Line, Tumor ,Genetics ,medicine ,Transcriptional regulation ,Humans ,Molecular Biology ,Gene ,DNA Primers ,Cisplatin ,Gene knockdown ,Base Sequence ,Tumor Suppressor Proteins ,Nuclear Proteins ,Tumor Protein p73 ,DNA-Binding Proteins ,Gene Expression Regulation ,Drug Resistance, Neoplasm ,Trans-Activators ,Cancer research ,Carcinogenesis ,Protein Binding ,medicine.drug - Abstract
Zinc-finger protein 143 (ZNF143) is a human homolog of Xenopus transcriptional activator staf that is involved in selenocystyl tRNA transcription. We previously showed that ZNF143 expression is induced by treatment with DNA-damaging agents and that it preferentially binds to cisplatin-modified DNA. In this study, the potential function of ZNF143 was investigated. ZNF143 was overexpressed in cisplatin-resistant cells. ZNF143 knockdown in prostate cancer caused increased sensitivity for cisplatin, but not for oxaliplatin, etoposide and vincristine. We also showed that ZNF143 is associated with tumor suppressor gene product p73 but not with p53. p73 could stimulate the binding of ZNF143 to both ZNF143 binding site and cisplatin-modified DNA, and modulate the function of ZNF143. We provide a direct evidence that both Rad51 and flap endonuclease-1 are target genes of ZNF143 and overexpressed in cisplatin-resistant cells. Taken together, these experiments demonstrate that an interplay of ZNF143, p73 and ZNF143 target genes is involved in DNA repair gene expression and cisplatin resistance.
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- 2007
11. Akt-dependent nuclear localization of Y-box-binding protein 1 in acquisition of malignant characteristics by human ovarian cancer cells
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Tatsu Shimoyama, Michihiko Kuwano, Abbas Fotovati, Yuji Basaki, Hiroto Izumi, Kimitoshi Kohno, Yuichiro Maruyama, Mayumi Ono, Kazuto Nishio, Shinji Oie, Kazuko Sakai, Fumihito Hosoi, and Yoshinao Oda
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Male ,Receptors, CXCR4 ,Cancer Research ,Transcription, Genetic ,Blotting, Western ,Transplantation, Heterologous ,Mice, Nude ,Biology ,medicine.disease_cause ,Mice ,Gene expression ,Biomarkers, Tumor ,Tumor Cells, Cultured ,Genetics ,medicine ,Animals ,Humans ,RNA, Small Interfering ,Molecular Biology ,Protein kinase B ,PI3K/AKT/mTOR pathway ,Oligonucleotide Array Sequence Analysis ,Cell Nucleus ,Ovarian Neoplasms ,Mice, Inbred BALB C ,Gene knockdown ,Gene Expression Profiling ,Nuclear Proteins ,Y box binding protein 1 ,Cell cycle ,DNA-Binding Proteins ,Gene Expression Regulation, Neoplastic ,Protein Transport ,Cancer cell ,Cancer research ,Female ,Y-Box-Binding Protein 1 ,Multidrug Resistance-Associated Proteins ,Carcinogenesis ,Proto-Oncogene Proteins c-akt - Abstract
Y-box-binding protein 1 (YB-1), which is a member of the DNA-binding protein family containing a cold-shock domain, has pleiotropic functions in response to various environmental stimuli. As we previously showed that YB-1 is a global marker of multidrug resistance in ovarian cancer and other tumor types. To identify YB-1-regulated genes in ovarian cancers, we investigated the expression profile of YB-1 small-interfering RNA (siRNA)-transfected ovarian cancer cells using a high-density oligonucleotide array. YB-1 knockdown by siRNA upregulated 344 genes, including MDR1, thymidylate synthetase, S100 calcium binding protein and cyclin B, and downregulated 534 genes, including CXCR4, N-myc downstream regulated gene 1, E-cadherin and phospholipase C. Exogenous serum addition stimulated YB-1 translocation from the cytoplasm to the nucleus, and treatment with Akt inhibitors as well as Akt siRNA and integrin-linked kinase (ILK) siRNA specifically blocked YB-1 nuclear localization. Inhibition of Akt activation downregulated CXCR4 and upregulated MDR1 (ABCB1) gene expression. Administration of Akt inhibitor resulted in decrease in nuclear YB-1-positive cancer cells in a xenograft animal model. Akt activation thus regulates the nuclear translocation of YB-1, affecting the expression of drug-resistance genes and other genes associated with the malignant characteristics in ovarian cancer cells. Therefore, the Akt pathway could be a novel target of disrupting the nuclear translocation of YB-1 that has important implications for further development of therapeutic strategy against ovarian cancers.
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- 2006
12. Expression of Y-box-binding protein dbpC/contrin, a potentially new cancer/testis antigen
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Hiroto Izumi, Akihide Tanimoto, Yasuyuki Sasaguri, Takeshi Uchiumi, Kimitoshi Kohno, Yukari Kohno, Shohei Shimajiri, and Yasumasa Matsuki
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Adult ,Male ,cancer stem cells ,Cancer Research ,Pathology ,medicine.medical_specialty ,Placenta ,RNA-binding protein ,Dysgerminoma ,Biology ,human tumours ,Testicular Neoplasms ,Antigen ,Antigens, Neoplasm ,Cancer stem cell ,medicine ,Humans ,Child ,Molecular Diagnostics ,Transcription factor ,Ovarian Neoplasms ,Gene Expression Profiling ,Binding protein ,RNA-Binding Proteins ,Middle Aged ,dbpC/contrin ,Immunohistochemistry ,Seminoma ,Trophoblasts ,Gene expression profiling ,Germ Cells ,Oncology ,Cancer research ,cancer/testis antigen ,Cancer/testis antigens ,Female - Abstract
Y-box-binding proteins are members of the human cold-shock domain protein superfamily, which includes dbpA, dbpB/YB-1, and dbpC/contrin. dbpC/contrin is a germ cell-specific Y-box-binding protein and is suggested to function as a nuclear transcription factor and RNA-binding protein in the cytoplasm. Whereas ubiquitous dbpB/YB-1 expression has been well studied in various types of human carcinomas as a prognostic or predictive marker, the dbpC/contrin expression in human tumour cells has not been reported. In this report, we provide the first evidence showing that dbpC was highly expressed in human testicular seminoma and ovarian dysgerminomas, and in carcinomas in other tissues and that its expression in normal tissues is nearly restricted to germ cells and placental trophoblasts. These results indicate that dbpC/contrin would be a potentially novel cancer/testis antigen.
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- 2006
13. Y-box binding protein 1 enhances DNA topoisomerase 1 activity and sensitivity to camptothecin via direct interaction
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Ke-Yong Wang, Yun-peng Liu, Yoshifumi Nakayama, Hiroto Izumi, Ken-ichi Ito, Hidetaka Uramoto, Kimitoshi Kohno, Zhi Li, and Ying Wu
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Cancer Research ,Y-box binding protein 1 ,Down-Regulation ,Eukaryotic DNA replication ,Protein interaction domains and motifs ,Topoisomerase-I Inhibitor ,Transfection ,Antioxidants ,Catalysis ,chemistry.chemical_compound ,Cell Line, Tumor ,medicine ,Topoisomerase 1 ,Humans ,Protein–DNA interaction ,Binding Sites ,biology ,Research ,Topoisomerase ,Y box binding protein 1 ,Acetylcysteine ,Enzyme Activation ,Gene Expression Regulation, Neoplastic ,Oxidative Stress ,DNA Topoisomerases, Type I ,Oncology ,chemistry ,Biochemistry ,Drug Resistance, Neoplasm ,Drug resistance ,biology.protein ,Nucleic Acid Conformation ,Camptothecin ,RNA Interference ,Y-Box-Binding Protein 1 ,Topoisomerase I Inhibitors ,DNA ,Protein Binding ,medicine.drug - Abstract
Background The Y-box binding protein 1 (YB-1) possesses pleiotropic functions through its interactions with various cellular proteins, and its high expression levels make it a potential useful prognostic biomarker for cancer cells. Eukaryotic DNA topoisomerases, such as DNA topoisomerase 1 (TOPO1) and DNA topoisomerase 2 (TOPO2), are the essential DNA metabolism regulators that usually overexpressed in cancer cells, and multiple proteins have been reported to regulate the enzyme activity and the clinical efficacy of their inhibitors. The present study unraveled the interaction of YB-1 with TOPO1, and further investigated the related function and potential mechanisms during the interaction. Methods The direct association of TOPO1 with specific domain of YB-1 was explored by co-immunoprecipitation and GST pull-down assays. The interaction function was further clarified by DNA relaxation assays, co-immunoprecipitation and WST-8 assays with in vitro gain- and loss- of function models. Results We found that YB-1 interacts directly with TOPO1 (but not with TOPO2) and promotes TOPO1 catalytic activity. Interactions between YB-1 and TOPO1 increased when cancer cells were treated with the TOPO1 inhibitor, camptothecin (CPT), but not with the TOPO2 inhibitor, adriamycin (ADM). Furthermore, we found that the interaction is prevented by pretreatment with the antioxidant agent, N-acetyl cysteine, and that YB-1 downregulation renders cells resistant to CPT. Conclusions Our findings suggest that nuclear YB-1 serves as an intracellular promoter of TOPO1 catalytic activity that enhances CPT sensitivity through its direct interaction with TOPO1.
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- 2014
14. Binding of RNA to p53 regulates its oligomerization and DNA-binding activity
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Takeshi Yoshida, Yoichiro Yoshida, Hiroshi Ishiguchi, Takayuki Torigoe, Hiroto Izumi, Hideaki Itoh, and Kimitoshi Kohno
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Male ,Cancer Research ,Tumor suppressor gene ,RNase P ,Protein Serine-Threonine Kinases ,Biology ,medicine.disease_cause ,Phosphoserine ,Structure-Activity Relationship ,chemistry.chemical_compound ,Biopolymers ,Cell Line, Tumor ,Genetics ,medicine ,Humans ,Phosphorylation ,Casein Kinase II ,Molecular Biology ,chemistry.chemical_classification ,RNA ,DNA ,Ribonuclease, Pancreatic ,Neoplasm Proteins ,Protein Structure, Tertiary ,Cell biology ,Enzyme ,chemistry ,Biochemistry ,biology.protein ,Female ,Pancreatic ribonuclease ,Cisplatin ,Tumor Suppressor Protein p53 ,Carcinogenesis ,Dimerization ,Protein Processing, Post-Translational ,Protein Binding - Abstract
The C-terminus of p53 is responsible for maintaining the latent, non-DNA-binding form of p53. However, the mechanism by which the C-terminus regulates DNA binding is not yet fully understood. We show here that p53 interacts with RNA via its C-terminal domain and that disruption of this interaction, by RNase A treatment, truncation or phosphorylation of the C-terminus, restores DNA-binding activity. Furthermore, the oligomerization of p53 is significantly enhanced by disrupting the interaction between p53 and RNA. These findings suggest that binding of RNA to p53 is involved in the mechanism of p53 latency.
- Published
- 2004
15. Erratum to: Strong expression of polypeptide N-acetylgalactosaminyltransferase 3 independently predicts shortened disease-free survival in patients with early stage oral squamous cell carcinoma
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Yoshikazu Harada, Hiroto Izumi, Hirotsugu Noguchi, Akihiro Kuma, Yuichiro Kawatsu, Tomoko Kimura, Shohei Kitada, Hidetaka Uramoto, Ke-Yong Wang, Yasuyuki Sasaguri, Hiroshi Hijioka, Akihiko Miyawaki, Ryoichi Oya, Toshiyuki Nakayama, Kimitoshi Kohno, and Sohsuke Yamada
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General Medicine - Published
- 2015
16. [Untitled]
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Catrin Molander, Keiko Funa, Mitsuhiro Ohta, Anders Hackzell, and Hiroto Izumi
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Transactivation ,Upstream activating sequence ,Transcription (biology) ,Chemistry ,Response element ,Genetics ,CAAT box ,Promoter ,General Medicine ,Binding site ,Molecular Biology ,Psychological repression ,Molecular biology - Abstract
The mouse PDGF β-receptor promoter is tightly controlled by NF-Y that binds to a CCAAT box located upstream of the initiation site [1, 2]. In this report, we show that Sp1 plays an essential role in the PDGF β-receptor transcription. Within the upstream GC rich area there are two Sp1 binding sites located in close proximity to the CCAAT box. Deletion of the GC rich region resulted in a 50% decrease of the transcriptional activity of the promoter, and a complete loss of its responsiveness to over-expression of Sp1. There was an additive effect between NF-Y and Sp1 in reporter activity when they were co-transfected together with the promoter-reporter construct. Furthermore, transfection of NF-Y failed to enhance transcriptional activity when the Sp1 binding sites were deleted from the promoter, suggesting an important role for Sp1 in this NF-Y controlled transcription. We have recently reported that c-Myc represses PDGF β-receptor transcription through its interference with the transactivation activity of NF-Y [3]. In the case of p21waf1/cip1 transcription, c-Myc was shown to repress its transcription by sequestering Sp1 [4]. However, we could not find any effect of Sp1 in the c-Myc-mediated repression on the PDGF β-receptor promoter, since the deletion of Sp1 binding sites could not attenuate the repression by c-Myc on the promoter activity.
- Published
- 2001
17. Direct interaction of p53 with the Y-box binding protein, YB-1: a mechanism for regulation of human gene expression
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Takashi Okamoto, Tomoko Ise, Hiroshi Takano, Hiroto Izumi, Takeshi Uchiumi, Kimitoshi Kohno, Toshihiro Imamura, and Michihiko Kuwano
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Transcriptional Activation ,Therapeutic gene modulation ,Cancer Research ,Biology ,SYT1 ,Consensus Sequence ,Gene expression ,Tumor Cells, Cultured ,Genetics ,Humans ,Molecular Biology ,Sequence Deletion ,Regulator gene ,Regulation of gene expression ,Reporter gene ,YY1 ,Nuclear Proteins ,Oligonucleotides, Antisense ,Y box binding protein 1 ,Molecular biology ,Protein Structure, Tertiary ,DNA-Binding Proteins ,NFI Transcription Factors ,CCAAT-Enhancer-Binding Proteins ,Y-Box-Binding Protein 1 ,Tumor Suppressor Protein p53 ,Transcription Factors - Abstract
The Y-box binding protein, YB-1, belongs to a family of multifunctional proteins which regulate gene expression on both transcriptional and translational levels. The tumor suppressor gene p53 displays growth suppressive properties by regulating gene expression through transcriptional regulation. We now demonstrate that YB-1 directly interacts with p53 using an in vitro pull-down assay. Using immunochemical co-precipitation methods, we also found that the two proteins are bound in vivo. Deletion analysis showed that three independent domains of YB-1, one at the N-terminal and two at the C-terminal, interact with p53. Conversely, a 14 amino acid sequence at the C-terminal of p53 was required for its interaction with YB-1. Gel mobility shift assays showed that the interaction of YB-1 with p53 stimulated the sequence-specific DNA binding of p53 to its consensus sequence. By contrast, this interaction inhibited the binding of YB-1. Using a p53-responsive p21 promoter linked to a reporter gene, it can be shown that antisense expression of YB-1 inhibits the induction of this promoter by p53 in transient transfection assays. These findings delineate a straightforward mechanism for gene expression through p53-YB-1 interaction.
- Published
- 2000
18. [Untitled]
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Kimitoshi Kohno, Michihiko Kuwano, Mayumi Ono, Takeshi Okamoto, Daisuke Goto, and Hiroto Izumi
- Subjects
Cancer Research ,Vascular endothelial growth factor A ,Paracrine signalling ,Vascular endothelial growth factor C ,Physiology ,Angiogenesis ,Clinical Biochemistry ,Cancer research ,Tumor necrosis factor alpha ,Interleukin 8 ,Biology ,Autocrine signalling ,Vascular endothelial growth inhibitor - Abstract
Angiogenic stimuli induce tubular morphogenesis and angiogenesis in vascular endothelial cells, but these cells are highly vulnerable to cytokines, oxidative stress, and genotoxic anticancer agents. A transcription factor, NF-κB, is involved in the protection against apoptosis and in angiogenesis in response to stimuli that could induce cell death. NF-κB was specifically activated by the genotoxic anticancer therapeutic agents etoposide and doxorubicin, but not by bleomycin, mitomycin C and cisplatin, in human vascular endothelial cells in three independent assay systems: nuclear translocation of NF-κB, binding of NF-κB to its consensus sequence, and NF-κB -dependent transcription. Exposure to etoposide and doxorubicin induced tubular morphogenesis by vascular endothelial cells in type I collagen gel at rates comparable to tumor necrosis factor-α. Co-administration of NF-κB antisense oligonucleotides inhibited the angiogenesis by doxorubicin and etoposide. In contrast, bleomycin, mitomycin C, and cisplatin did not induce angiogenesis. An angiogenic factor, interleukin 8, was dramatically induced in vascular endothelial cells treated with doxorubicin, but not in cells treated with cisplatin. Co-administration of anti-interleukin 8 antibody almost completely blocked the doxorubicin-induced angiogenesis in vitro, suggesting a paracrine/autocrine control through drug-induced angiogenic factor(s). The presence or absence of NF-κB activation may have an essential role in tubular morphogenesis by vascular endothelial cells during chemotherapeutic treatment, possibly through interleukin 8.
- Published
- 1998
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