17 results on '"Keen, Judith C."'
Search Results
2. Genome-wide SNP assay reveals structural genomic variation, extended homozygosity and cell-line induced alterations in normal individuals
- Author
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Simon-Sanchez, Javier, Scholz, Sonja, Fung, Hon-Chung, Matarin, Mar, Hernandez, Dena, Gibbs, J. Raphael, Britton, Angela, de Vrieze, Fabienne Wavrant, Peckham, Elizabeth, Gwinn-Hardy, Katrina, Crawley, Anthony, Keen, Judith C., Nash, Josefina, Borgaonkar, Digamber, Hardy, John, and Singleton, Andrew
- Published
- 2007
3. Characterization of a novel PMA-inducible pathway of interleukin-13 gene expression in T cells
- Author
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Keen, Judith C., Cianferoni, Antonella, Florio, Giovanni, Guo, Jia, Chen, Rongbing, Roman, Jessica, Wills-Karp, Marsha, Casolaro, Vincenzo, and Georas, Steve N.
- Published
- 2006
4. Assessing the Training and Research Environment for Genomics, Bioinformatics, and Immunology in Radiation Oncology.
- Author
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Mouw, Kent W., Beck, Tyler F., Keen, Judith C., and Dicker, Adam P.
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GENOMICS ,BIOINFORMATICS ,IMMUNOLOGY ,RADIATION ,ONCOLOGY ,ONCOLOGISTS - Abstract
Purpose: To assess radiation oncologists' perceptions of training and research opportunities in the fields of genomics, bioinformatics, and immunology. Materials and Methods: A 13-item electronic survey was sent to 101 radiation oncology department chairs and administrators. A separate 30-item electronic survey was sent to 132 members of the American Society for Radiation Oncology Science Council as well as to 565 members of the Association of Residents in Radiation Oncology. Survey responses were collected, and results were analyzed using descriptive statistics. Results: Twenty-six department chairs and 91 general respondents submitted responses. Among general respondents, 69% were current trainees and 31% had completed training. The majority of respondents (92%) were affiliated with an academic/university main campus. Approximately half of respondents (43% to 53%) reported no prior formal training in bioinformatics, genomics, or immunology. More than half of department chairs (54% to 58%) and general respondents (57% to 63%) thought that current training opportunities in these areas were absolutely or moderately insufficient. A majority of respondents (53% to 65%) thought that additional training in these areas would provide opportunity for career advancement, and 80% could identify a current or future research project that additional training in these fields would allow them to pursue. More than half of respondents expressed interest in attending a formal training course, and the majority of department chairs (22 of 26 [85%]) reported that they would probably or definitely send trainees or faculty members to a formal training course. Conclusion: Among radiation oncologists surveyed, there is a perceived lack of current training opportunities in bioinformatics, genomics, and immunology. A majority of respondents reported an interest in obtaining additional training in these areas and believed that training would provide opportunity for career advancement. [ABSTRACT FROM AUTHOR]
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- 2018
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5. Responses to the 2017 “1 Million Gray Question”: ASTRO Membership's Opinions on the Most Important Research Question Facing Radiation Oncology
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Dominello, Michael M., Keen, Judith C., Beck, Tyler F., Bayouth, John, Knisely, Jonathan, Carlson, David J., Mendonca, Marc S., Mian, Omar, Brock, Kristy K., Anscher, Mitchell, Hugo, Geoffrey, Moros, Eduardo G., Singh, Anurag K., and Yu, James B.
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- 2018
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6. Breast Cancer Cell Line Development and Authentication
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Keen, Judith C.
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Medical / Prosthesis - Abstract
Breast Cancer Cell Line Development and Authentication
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- 2011
7. Distinct signal requirement for IL-4 and IL-13 expression
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Keen, Judith C., Viswanathan, Natarajan, Thomas, Burke, Jia, Guo, Antonella, Cianferoni, John, Schmidt, Casolaro, Vincenzo, Marsha Wills Karp, and Georas, Steve N.
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- 2001
8. Dissociation of the effects of salicylates on IL-4 gene expression and NFAT activation in human T cells
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Antonella, Cianferoni, Schroeder, John T., Keen, Judith C., Schmidt, John W., Georas, Steve N., and Casolaro, Vincenzo
- Published
- 2000
9. The ASTRO Research Portfolio: Where Do We Go From Here?
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Yu, James B., Beck, Tyler F., Anscher, Mitchell S., Baschnagel, Andrew M., Brock, Kristy K., Carlson, David J., Dominello, Michael M., Kimple, Randall J., Knisely, Jonathan P.S., Mendonca, Marc S., Mian, Omar Y., Singh, Anurag K., Moros, Eduardo G., and Keen, Judith C.
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- 2019
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10. pp32 (ANP32A) Expression Inhibits Pancreatic Cancer Cell Growth and Induces Gemcitabine Resistance by Disrupting HuR Binding to mRNAs.
- Author
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Williams, Timothy K., Costantino, Christina L., Bildzukewicz, Nikolai A., Richards, Nathan G., Rittenhouse, David W., Einstein, Lisa, Cozzitorto, Joseph A., Keen, Judith C., Dasgupta, Abhijit, Gorospe, Myriam, Gonye, Gregory E., Yeo, Charles J., Witkiewicz, Agnieszka K., and Brody, Jonathan R.
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GENE expression ,PANCREATIC cancer ,CANCER cell growth ,MESSENGER RNA ,CANCER chemotherapy ,MICROBIOLOGICAL assay ,CYTARABINE ,CYTOPLASM ,LYMPHATIC metastasis ,SUPPRESSOR cells - Abstract
The expression of protein phosphatase 32 (PP32, ANP32A) is low in poorly differentiated pancreatic cancers and is linked to the levels of HuR (ELAV1), a predictive marker for gemcitabine response. In pancreatic cancer cells, exogenous overexpression of pp32 inhibited cell growth, supporting its long-recognized role as a tumor suppressor in pancreatic cancer. In chemotherapeutic sensitivity screening assays, cells overexpressing pp32 were selectively resistant to the nucleoside analogs gemcitabine and cytarabine (ARA-C), but were sensitized to 5-fluorouracil; conversely, silencing pp32 in pancreatic cancer cells enhanced gemcitabine sensitivity. The cytoplasmic levels of pp32 increased after cancer cells are treated with certain stressors, including gemcitabine. pp32 overexpression reduced the association of HuR with the mRNA encoding the gemcitabine-metabolizing enzyme deoxycytidine kinase (dCK), causing a significant reduction in dCK protein levels. Similarly, ectopic pp32 expression caused a reduction in HuR binding of mRNAs encoding tumor-promoting proteins (e.g., VEGF and HuR), while silencing pp32 dramatically enhanced the binding of these mRNA targets. Low pp32 nuclear expression correlated with high-grade tumors and the presence of lymph node metastasis, as compared to patients' tumors with high nuclear pp32 expression. Although pp32 expression levels did not enhance the predictive power of cytoplasmic HuR status, nuclear pp32 levels and cytoplasmic HuR levels associated significantly in patient samples. Thus, we provide novel evidence that the tumor suppressor function of pp32 can be attributed to its ability to disrupt HuR binding to target mRNAs encoding key proteins for cancer cell survival and drug efficacy. [ABSTRACT FROM AUTHOR]
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- 2010
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11. Polyamine Analogues Down-regulate Estrogen Receptor α Expression in Human Breast Cancer Cells.
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Yi Huang, Keen, Judith C., Pledgie, Allison, Marton, Laurence J., Tao Zhu, Sukumar, Saraswati, Ben Ho Park, Blair, Brian, Brenner, Keith, Casero Jr., Robert A., and Davidson, Nancy E.
- Subjects
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CANCER cells , *POLYAMINES , *ESTROGEN , *CELL receptors , *BREAST cancer - Abstract
The critical role of polyamines in cell growth has led to the development of a number of agents that interfere with polyamine metabolism including a novel class of polyamine analogues, oligoamines. Here we demonstrate that oligoamines specifically suppress the mRNA and protein expression of estrogen receptor α (ERα) and ERα target genes in ER-positive human breast cancer cell lines, whereas neither ERβ nor other steroid hormonal receptors are affected by oligoamines. The constitutive expression of a cytomegalovirus promoter-driven exogenous ERα in ER-negative MDA-MB-231 human breast cancer cells was not altered by oligoamines, suggesting that oligoamines specifically suppress ERα transcription rather than affect mRNA or protein stability. Further analysis demonstrated that oligoamines disrupted the DNA binding activity of Sp1 transcription factor family members to an ERα minimal promoter element containing GC/CA-rich boxes. Treatment of MDA-MB-231 cells with the JNK-specific inhibitor SP600125 or expression of the c-Jun dominant negative inhibitor TAM67 blocked the oligoamine-activated JNK/c-Jun pathway and enhanced oligoamine-inhibited ERα expression, suggesting that AP-1 is a positive regulator of ERα expression and that oligoamine-activated JNK/AP-1 activity may antagonize the down-regulation of ERα induced by oligoamines. Taken together, these results suggest a novel antiestrogenic mechanism for specific polyamine analogues in human breast cancer cells. [ABSTRACT FROM AUTHOR]
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- 2006
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12. Protein Phosphatase 2A Regulates Estrogen Receptor α (ER) Expression through Modulation of ER mRNA Stability.
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Keen, Judith C., Qun Zhou, Ben Ho Park, Pettit, Catherine, Mack, Kelly M., Blair, Brian, Brenner, Keith, and Davidson, Nancy E.
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PHOSPHOPROTEIN phosphatases , *ESTROGEN receptors , *PHOSPHATASES , *MESSENGER RNA , *SERINE , *ESTERASES - Abstract
Protein phosphatase 2A (PP2A) is a ubiquitously expressed member of the serine-threonine phosphatase family that is involved in regulation of many cellular processes including transcription, translation, cellular metabolism, and apoptosis. Because of a correlation between PP2A and estrogen receptor α (ER) expression in several human breast cancer cell lines, the effect of PP2A on regulation of ER expression in the human breast cancer cell line MCF-7 was studied. Inhibition of PP2A using the pharmacologic inhibitor okadaic acid at 250 nM for 16 h resulted in a 60% reduction in PP2A activity in MCF-7 cells concurrent with a 75% reduction in ER mRNA and protein expression. Similar results were obtained with a small interfering RNA probe that specifically inhibited PP2A expression. ER promoter studies showed that regulation of ER through the PP2A pathway did not occur through transcriptional activation. Rather, PP2A mediated ER expression through modulation of ER mRNA stability through degradation of ER mRNA, reversible with concomitant treatment with the proteasomal inhibitor MG 132. These data suggest a novel pathway controlling ER expression resulting from the activation of PP2A, potentially providing a novel therapeutic target. [ABSTRACT FROM AUTHOR]
- Published
- 2005
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13. The 'RNA-binding ome': future implications for chemotherapeutic efficacy.
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Brody JR, Witkiewicz AK, Yeo CJ, Gorospe M, and Keen JC
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- Animals, Humans, Antineoplastic Agents therapeutic use, Genome, Neoplasms drug therapy, Neoplasms genetics, RNA metabolism, RNA-Binding Proteins genetics
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- 2009
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14. The role of HuR in gemcitabine efficacy in pancreatic cancer: HuR Up-regulates the expression of the gemcitabine metabolizing enzyme deoxycytidine kinase.
- Author
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Costantino CL, Witkiewicz AK, Kuwano Y, Cozzitorto JA, Kennedy EP, Dasgupta A, Keen JC, Yeo CJ, Gorospe M, and Brody JR
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- Antigens, Surface genetics, Antimetabolites, Antineoplastic therapeutic use, Biomarkers, Tumor genetics, Biomarkers, Tumor physiology, Cytarabine therapeutic use, Deoxycytidine pharmacokinetics, Deoxycytidine therapeutic use, Deoxycytidine Kinase metabolism, Drug Resistance, Neoplasm genetics, ELAV Proteins, ELAV-Like Protein 1, Gene Expression Regulation, Neoplastic drug effects, Humans, Inactivation, Metabolic genetics, RNA-Binding Proteins genetics, Time Factors, Treatment Outcome, Tumor Cells, Cultured, Up-Regulation drug effects, Gemcitabine, Antigens, Surface physiology, Carcinoma, Pancreatic Ductal drug therapy, Carcinoma, Pancreatic Ductal genetics, Deoxycytidine analogs & derivatives, Deoxycytidine Kinase genetics, Pancreatic Neoplasms drug therapy, Pancreatic Neoplasms genetics, RNA-Binding Proteins physiology
- Abstract
RNA-binding protein HuR binds U- or AU-rich sequences in the 3'-untranslated regions of target mRNAs, stabilizing them and/or modulating their translation. Given the links of HuR with cancer, we studied the consequences of modulating HuR levels in pancreatic cancer cells. HuR-overexpressing cancer cells, in some instances, are roughly up to 30-fold more sensitive to treatment with gemcitabine, the main chemotherapeutic component of treatment regimens for pancreatic ductal adenocarcinoma (PDA), compared with control cells. In pancreatic cancer cells, HuR associates with deoxycytidine kinase (dCK) mRNA, which encodes the enzyme that metabolizes and thereby activates gemcitabine. Gemcitabine exposure to pancreatic cancer cells enriches the association between HuR and dCK mRNA and increases cytoplasmic HuR levels. Accordingly, HuR overexpression elevates, whereas HuR silencing reduces, dCK protein expression in pancreatic cancer cells. In a clinical correlate study of gemcitabine treatment, we found a 7-fold increase in risk of mortality in PDA patients with low cytoplasmic HuR levels compared with patients with high HuR levels, after adjusting for other treatments and demographic variables. These data support the notion that HuR is a key mediator of gemcitabine efficacy in cancer cells, at least in part through its ability to regulate dCK levels posttranscriptionally. We propose that HuR levels in PDA modulate the therapeutic efficacy of gemcitabine, thus serving as a marker of the clinical utility of this common chemotherapeutic agent and a potential target for intervention in pancreatic cancer.
- Published
- 2009
- Full Text
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15. Polyamine analogues down-regulate estrogen receptor alpha expression in human breast cancer cells.
- Author
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Huang Y, Keen JC, Pledgie A, Marton LJ, Zhu T, Sukumar S, Park BH, Blair B, Brenner K, Casero RA Jr, and Davidson NE
- Subjects
- Cell Line, Tumor, Cytomegalovirus genetics, Estrogen Receptor Modulators metabolism, Humans, Polyamines metabolism, Promoter Regions, Genetic, RNA, Messenger metabolism, Sp1 Transcription Factor metabolism, Breast Neoplasms metabolism, Down-Regulation, Estrogen Receptor alpha biosynthesis, Gene Expression Regulation, Neoplastic, Polyamines chemistry
- Abstract
The critical role of polyamines in cell growth has led to the development of a number of agents that interfere with polyamine metabolism including a novel class of polyamine analogues, oligoamines. Here we demonstrate that oligoamines specifically suppress the mRNA and protein expression of estrogen receptor alpha (ERalpha) and ERalpha target genes in ER-positive human breast cancer cell lines, whereas neither ERbeta nor other steroid hormonal receptors are affected by oligoamines. The constitutive expression of a cytomegalovirus promoter-driven exogenous ERalpha in ER-negative MDA-MB-231 human breast cancer cells was not altered by oligoamines, suggesting that oligoamines specifically suppress ERalpha transcription rather than affect mRNA or protein stability. Further analysis demonstrated that oligoamines disrupted the DNA binding activity of Sp1 transcription factor family members to an ERalpha minimal promoter element containing GC/CA-rich boxes. Treatment of MDA-MB-231 cells with the JNK-specific inhibitor SP600125 or expression of the c-Jun dominant negative inhibitor TAM67 blocked the oligoamine-activated JNK/c-Jun pathway and enhanced oligoamine-inhibited ERalpha expression, suggesting that AP-1 is a positive regulator of ERalpha expression and that oligoamine-activated JNK/AP-1 activity may antagonize the down-regulation of ERalpha induced by oligoamines. Taken together, these results suggest a novel antiestrogenic mechanism for specific polyamine analogues in human breast cancer cells.
- Published
- 2006
- Full Text
- View/download PDF
16. Epigenetic regulation of protein phosphatase 2A (PP2A), lymphotactin (XCL1) and estrogen receptor alpha (ER) expression in human breast cancer cells.
- Author
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Keen JC, Garrett-Mayer E, Pettit C, Mack KM, Manning J, Herman JG, and Davidson NE
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- Acetylation drug effects, Azacitidine pharmacology, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Chemokines, C, DNA Modification Methylases antagonists & inhibitors, Decitabine, Estrogen Receptor alpha metabolism, Female, Gene Expression Profiling, Gene Expression Regulation, Neoplastic drug effects, Histone Deacetylase Inhibitors, Humans, Hydroxamic Acids, Lymphokines metabolism, Oligonucleotide Array Sequence Analysis, Phosphoprotein Phosphatases metabolism, Protein Phosphatase 2, RNA, Messenger genetics, RNA, Messenger metabolism, RNA, Neoplasm genetics, RNA, Neoplasm metabolism, Receptors, Progesterone genetics, Receptors, Progesterone metabolism, Reverse Transcriptase Polymerase Chain Reaction, Sialoglycoproteins metabolism, Tumor Cells, Cultured, Azacitidine analogs & derivatives, Breast Neoplasms genetics, DNA Methylation, Epigenesis, Genetic, Estrogen Receptor alpha genetics, Lymphokines genetics, Phosphoprotein Phosphatases genetics, Sialoglycoproteins genetics
- Abstract
Absence of the estrogen receptor alpha (ER) in human breast cancer cells is an indicator of poor prognosis, and predictive of lack of response to hormonal therapy. Previous studies in our laboratory and others have shown that epigenetic regulation, including DNA methylation and histone deacetylation, are common mechanisms leading to ER gene silencing. Through the use of pharmacologic inhibitors, 5-aza 2'deoxycytidine (AZA) and Trichostatin A (TSA), we have shown that alterations in both of these mechanisms results in synergistic reexpression of ER mRNA and functional protein. These alterations may play a larger role in stimulation of cell signaling pathways leading to ER expression. We have utilized newly developed genome wide screening microarray techniques to identify gene(s) contributing to the hormone independent phenotype and AZA/TSA mediated ER expression. From this screen, we identified and confirmed expression of 4 candidate genes (PP2A, XCL1, THY1 and NBC4) as potential regulators of the hormone independent phenotype. Expression of two genes, XCL1 and PP2A, appeared to be correlated with ER expression. PP2A expression was not changed with ER degradation using ICI 182,780 whereas XCL1 expression decreased in the presence of AZA/TSA and ICI 182,780. This suggests that PP2A may be a determinant of ER expression while XCL1 appears to be ER responsive and downstream of ER expression. These gene products may be novel targets to be further explored in the development of new therapeutics for ER negative breast cancer.
- Published
- 2004
- Full Text
- View/download PDF
17. Regulation of polyamine analogue cytotoxicity by c-Jun in human MDA-MB-435 cancer cells.
- Author
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Huang Y, Keen JC, Hager E, Smith R, Hacker A, Frydman B, Valasinas AL, Reddy VK, Marton LJ, Casero RA Jr, and Davidson NE
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- Anthracenes pharmacology, Apoptosis drug effects, Breast Neoplasms genetics, Cell Division drug effects, Gene Expression Regulation, Neoplastic drug effects, Humans, Mutation genetics, Peptide Fragments biosynthesis, Peptide Fragments genetics, Phosphorylation drug effects, Proto-Oncogene Proteins c-fos biosynthesis, Proto-Oncogene Proteins c-jun biosynthesis, Proto-Oncogene Proteins c-jun genetics, Transfection, Tumor Cells, Cultured, Up-Regulation drug effects, Breast Neoplasms metabolism, Breast Neoplasms pathology, Peptide Fragments metabolism, Polyamines chemistry, Polyamines toxicity, Proto-Oncogene Proteins c-jun metabolism
- Abstract
Several polyamine analogues have efficacy against a variety of epithelial tumor models including breast cancer. Recently, a novel class of polyamine analogues designated as oligoamines has been developed. Here, we demonstrate that several representative oligoamine compounds inhibit in vitro growth of human breast cancer MDA-MB-435 cells. The activator protein-1 (AP-1) transcriptional factor family members, c-Jun and c-Fos, are up-regulated by oligoamines in MDA-MB-435 cells, suggesting a possible AP-1-dependent induction of apoptosis. However, the use of a novel c-Jun NH(2)-terminal kinase (JNK) inhibitor, SP600125, suggests that inhibition of c-Jun activity sensitized tumor cells to oligoamine-induced cell death. To directly test this hypothesis, cells were stably transfected with the dominant-negative mutant c-Jun (TAM67), which lacks the NH(2)-terminal transactivation domain. Cells overexpressing TAM67 exhibit normal growth kinetics but demonstrate a significantly increased sensitivity to oligoamine cytotoxicity and attenuated colony formation after oligoamine treatment. Furthermore, oligoamine treatment leads to more profound caspase-3 activation and poly(ADP-ribose) polymerase cleavage in TAM67 transfectants, suggesting that c-Jun acts as an antiapoptosis factor in MDA-MB-435 cells in response to oligoamine treatment. These findings indicate that oligoamine-inducible AP-1 plays a prosurvival role in oligoamine-treated MDA-MB-435 cells and that JNK/AP-1 might be a potential target for enhancing the therapeutic efficacy of polyamine analogues in human breast cancer.
- Published
- 2004
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