7 results on '"V Fernández-Soria"'
Search Results
2. Adenovirus E1A orchestrates the urokinase-plasminogen activator system and upregulates PAI-2 expression, supporting a tumor suppressor effect.
- Author
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Fernández-Soria V, Lleonart ME, Diaz-Fuertes M, Villuendas R, Sánchez-Prieto R, Fabra A, and Ramón Y Cajal S
- Subjects
- Adenoviridae physiology, Blotting, Western, Female, Gene Expression Profiling, Humans, Neoplasm Invasiveness, Neoplasm Metastasis, Oligonucleotide Array Sequence Analysis, Reverse Transcriptase Polymerase Chain Reaction, Tumor Cells, Cultured, Up-Regulation, Adenoviridae genetics, Adenovirus Early Proteins physiology, Breast Neoplasms pathology, Carcinoma pathology, Gene Expression Regulation, Neoplastic, Plasminogen Activator Inhibitor 1 biosynthesis
- Abstract
Invasiveness and metastatic potential are the two most important properties defining malignancy. The adeno-virus E1A (Ad-E1A) gene has a dual effect as a proliferative gene and as a tumor-suppressor gene, decreasing tumor growth and the metastatic potential of malignant cells. In order to study genes related with the antimetastatic effect of Ad-E1A in human cells, we performed a microarray analysis using OncoChiptrade mark. In three independent experiments, NIH3T3, IMR90 and MDA MB 435 cells were infected with pLPC retroviruses carrying the adenovirus 12S E1A gene or the GFP gene. We analyzed cDNA expression by using the CNIO OncoChipTM, a cDNA microarray containing a total of 6386 genes represented by 7237 clones. uPA, uPAr, tPA, PAI-1 and PAI-2 were also studied at RNA and protein levels. Microarrays of cDNA expression, RT-PCR and Western blot performed in IMR90 E1A-expressing cells showed downregulation of uPA, uPAr, tPA, PAI-1 and upregulation of PAI-2. These results were confirmed in NIH3T3 and MDA MB 435 breast carcinoma cells, with PAI-2 upregulation by RT-PCR and Western blot. In addition, zymographic analysis demonstrated that E1A expression greatly reduced the gelatinase activity of the pro-MMP2 and -MMP9 proteins. We propose that adenovirus E1A may orchestrate the expression of most members of the urokinase-plasminogen activation system, downregulating potentially invasive genes and upregulating PAI-2, which is associated with a better prognosis in human tumors.
- Published
- 2006
3. Oncogene HER-2 in canine mammary gland carcinomas: an immunohistochemical and chromogenic in situ hybridization study.
- Author
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Martin de las Mulas J, Ordás J, Millán Y, Fernández-Soria V, and Ramón y Cajal S
- Subjects
- Animals, Disease Models, Animal, Dog Diseases pathology, Dogs, Female, Gene Amplification, Humans, Immunohistochemistry veterinary, In Situ Hybridization veterinary, Mammary Neoplasms, Animal pathology, Dog Diseases genetics, Gene Expression Regulation, Neoplastic, Mammary Neoplasms, Animal genetics, Receptor, ErbB-2 biosynthesis, Receptor, ErbB-2 genetics
- Abstract
Immunohistochemical (IHC) HER-2/neu protein overexpression was found in 17.6% of canine mammary gland carcinomas, a percentage similar to that observed in human breast carcinoma, but there was no gene amplification by chromogenic in situ hybridization (CISH). Canine mammary carcinoma would be a suitable natural model of that subset of human breast carcinomas with HER-2 protein overexpression without gene amplification.
- Published
- 2003
- Full Text
- View/download PDF
4. Adenovirus E1a protein enhances the cytotoxic effects of the herpes thymidine kinase-ganciclovir system.
- Author
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Parada C, Hernández Losa J, Guinea J, Sánchez-Arévalo V, Fernández Soria V, Alvarez-Vallina L, Sánchez-Prieto R, and Ramón y Cajal S
- Subjects
- 3T3 Cells drug effects, 3T3 Cells pathology, Adenovirus E1A Proteins genetics, Animals, Cell Cycle genetics, Cisplatin pharmacology, Cyclin B metabolism, Cyclin B1, Drug Synergism, Genetic Engineering methods, HeLa Cells drug effects, HeLa Cells pathology, Humans, Mice, Retroviridae genetics, Simplexvirus genetics, Thymidine Kinase biosynthesis, Thymidine Kinase genetics, Tumor Cells, Cultured, Adenovirus E1A Proteins pharmacology, Antibiotics, Antineoplastic pharmacology, Ganciclovir pharmacology, Genetic Therapy methods, Simplexvirus enzymology, Thymidine Kinase pharmacology
- Abstract
Cancer gene therapy based on the use of suicide genes, such as the thymidine kinase gene, is not producing satisfactory results. Several approaches have been delineated to enhance the therapeutic responses, including augmentation of the bystander effect, the combination of the herpes simplex virus thymidine kinase-ganciclovir (HSVTK-GCV) system into replication competent adenoviruses and others. Moreover, because usually less than 20% of human malignant cells are in S-phase, the HSVTK-GCV system is not as efficient as expected. To increase the cytotoxic effects of the HSVTK-GCV system, we hypothesized that concomitant expression of E1a protein, which drives cells to proliferation and S-phase, could increase the effects of the HSVTK-GCV system. Several retroviruses were constructed carrying bicistronic sequences of TK and E1a 12S genes under the control of the CMV promoter. The constructions were tested in murine (NIH-3T3, MSC11A5) and human cells (IMR90, HeLa, MDA-MB435). A clear increase of the HSVTK-GCV system killing effect in nonconfluent cells was observed in the cells studied, especially in NIH-3T3, MSC11A5, IMR90, and MDA-MB435 expressing cells. In confluence, the NIH3T3 and IMR90 E1a-TK-expressing cells were also very sensitive and most malignant E1a-TK-expressing cells showed an irreversible G2-M cell cycle arrest. Moreover, the concomitant expression of adenovirus E1a and the HSVTK-GCV system increased the sensitivity to anticancer agents such as cisplatin. These results show that adenovirus E1a protein expression clearly enhances the cytotoxic effects of the HSVTK-GCV system and the response to treatment with cisplatin.
- Published
- 2003
- Full Text
- View/download PDF
5. Lack of HLA-G soluble isoforms in Graves-Basedow thyrocytes and complete cDNA sequence of the HLA-G*01012 allele.
- Author
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Castro MJ, Morales P, Catálfamo M, Fernández-Soria V, Suárez B, Varela P, Pérez-Blas M, Alvarez M, Jaraquemada D, and Arnaiz-Villena A
- Subjects
- Alleles, Alternative Splicing, Cell Line, Cells, Cultured, DNA, DNA, Complementary, Graves Disease genetics, HLA Antigens chemistry, HLA Antigens genetics, HLA-G Antigens, Histocompatibility Antigens Class I chemistry, Histocompatibility Antigens Class I genetics, Humans, Molecular Sequence Data, RNA, Messenger metabolism, Thyroid Gland cytology, Graves Disease immunology, HLA Antigens analysis, Histocompatibility Antigens Class I analysis, Thyroid Gland immunology
- Abstract
The presence of HLA-G mRNA has been studied in thyroid follicular cells from autoimmune patients with Graves' disease. Investigating the possible role of the expression of the HLA-G gene in tissue inflammation, we have found four of the six HLA-G mRNA isoforms described: G1, G2, G3 and G4, but not the soluble ones G5 and G6. Soluble G isoforms may be responsible for inducing tolerance and inflammation control and their absence in autoimmune thyroid follicular cells may induce failure of such control. In addition, the complete coding sequence of HLA-G*01012 has been obtained from thyrocytes and it shows only four synonymous changes with respect to the HLA-G*01011 allele; this further supports the existence of an evolutionary pressure for invariance on HLA-G genes.
- Published
- 1998
- Full Text
- View/download PDF
6. Mhc-E polymorphism in Pongidae primates: the same allele is found in two different species.
- Author
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Suárez B, Morales P, Castro MJ, Fernández-Soria V, Recio MJ, Pérez-Blas M, Alvarez M, Díaz-Campos N, and Arnaiz-Villena A
- Subjects
- Animals, Base Sequence, Cell Line, Transformed, DNA, Complementary, Gorilla gorilla immunology, HLA Antigens genetics, Histocompatibility Antigens Class I genetics, Hominidae genetics, Hominidae immunology, Humans, Molecular Sequence Data, Pan paniscus immunology, Pan troglodytes immunology, Phylogeny, Pongo pygmaeus immunology, Sequence Homology, Nucleic Acid, Species Specificity, HLA-E Antigens, Alleles, Gorilla gorilla genetics, Major Histocompatibility Complex, Pan paniscus genetics, Pan troglodytes genetics, Polymorphism, Genetic, Pongo pygmaeus genetics
- Abstract
Mhc-E intron 1, exon 2, intron 2, and exon 3 from pygmy chimpanzee (Pan paniscus), chimpanzee (Pan troglodytes), gorilla (Gorilla gorilla) and orangutan (Pongo pygmaeus) have been sequenced; six new Mhc-E alleles have been obtained but sequence changes are only placed either in introns or in synonymous exonic bases. One pygmy chimpanzee Mhc-E DNA sequence is identical to another sequence from chimpanzee; the fact that no variation is found also at the intronic level suggests that these two species of chimpanzee may have recently separated and/or that both of them might only represent subspecies. Mhc-E phylogenetic trees separate two evolutionary groups: Pongidae, including humans, and Cercopithecinae; this is also found by studying another non-classical class I gene, Mhc-G. The Mhc-E alleles' invariance at the protein level supports that strong selective forces are operating at the Mhc-E locus, as has also been found in both Cercopithecinae and humans. These allelic and evolutionary data suggest an altogether different functionality for HLA-E (and also HLA-G) compared with classical class I proteins: i.e., sending negative (tolerogenic) signals to NK and T cells.
- Published
- 1997
- Full Text
- View/download PDF
7. Allelic diversity at the primate Mhc-G locus: exon 3 bears stop codons in all Cercopithecinae sequences.
- Author
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Castro MJ, Morales P, Fernández-Soria V, Suarez B, Recio MJ, Alvarez M, Martín-Villa M, and Arnaiz-Villena A
- Subjects
- Alleles, Animals, Base Sequence, Biological Evolution, Exons, HLA-G Antigens, Humans, Introns, Macaca genetics, Molecular Sequence Data, Pan troglodytes genetics, Phylogeny, Polymorphism, Genetic, Sequence Alignment, Sequence Homology, Nucleic Acid, Cercopithecinae genetics, HLA Antigens genetics, Histocompatibility Antigens Class I genetics, Major Histocompatibility Complex
- Abstract
Twenty-seven major histocompatibility complex (Mhc)-G exon 2, exon 3, and exon 2 and 3 allelic sequences were obtained together with 12 different intron 2 sequences. Homo sapiens, Pan troglodytes, Pan paniscus, Gorilla gorilla, Pongo pygmaeus, Macaca fascicularis, Macaca mulatta, and Cercopithecus aethiops individuals were studied. Polymorphism does not follow the classical pattern of three hypervariable regions per domain and is found in all species studied; exon 3 (equivalent to the alpha 2 protein domain) shows stop codons in the Cercopithecinae group but not in the Pongidae and human groups. Dendrograms show that cotton top tamarin (Saguinus oedipus) Mhc-G sequences are closer to Homo sapiens and Pongidae than to Cercopithecinae, probably due to the stop codons existing at exon 3 of the latter. There is a clear trans-species evolution of allelism in Cercopithecinae and also in exon 2 of all the other apes studied, but a generation of allelism within each species may be present on exon 3 sequences. This discrepancy may be due to the preferential use of exon 2 over exon 3 at the mRNA splicing level within each species in order to obtain the appropriate functional G product. Mhc-G intron 2 shows conserved motifs in all species studied, particularly a 23 base pair deletion between positions 161 and 183 which is locus specific, and some of the invariant residues, important for peptide presentation, conserved in classical class I molecules from fish and reptiles to humans were not found in Mhc-G alleles; the intron 2 dendrogram also shows a particular pattern of allelism within each species. In summary, Mhc-G has substantial differences from other classical class I genes: polymorphism patterns, tissue distribution, gene structure, splicing variability, and probably an allelism variability within each species at exon 3. The G proteins may also be different. This indicates that the Mhc-G function may not be peptide presentation to the clonotypic T-cell receptor.
- Published
- 1996
- Full Text
- View/download PDF
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