Gene expression profiling by DNA microarray analysis in mouse embryonic fibroblasts transformed by rasV12 mutated protein and the E1A oncogene
| Autor: | Vasseur, Sophie, Malicet, Cédric, Calvo, Ezequiel L, Labrie, Claude, Berthezene, Patrice, Dagorn, Jean Charles, Iovanna, Juan Lucio |
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| Přispěvatelé: | Physiopathologie du stress pancréatique, Institut National de la Santé et de la Recherche Médicale (INSERM), Stress Cellulaire, Université de la Méditerranée - Aix-Marseille 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Molecular Endocrinology and Oncology Research Center, Laval University Medical center, Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), This work was supported by a grant from the Ligue Nationale Contre le Cancer (LNCC) and Association pour la Recherche sur le Cancer (ARC)., Maylin, Françoise |
| Rok vydání: | 2003 |
| Předmět: |
Down-Regulation
[SDV.CAN]Life Sciences [q-bio]/Cancer Oncogene Protein p21(ras) lcsh:RC254-282 MESH: Expressed Sequence Tags MESH: Down-Regulation MESH: Gene Expression Profiling Mice [SDV.CAN] Life Sciences [q-bio]/Cancer [SDV.BBM.GTP]Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] [SDV.BBM] Life Sciences [q-bio]/Biochemistry Molecular Biology Animals MESH: Animals [SDV.BBM]Life Sciences [q-bio]/Biochemistry Molecular Biology MESH: Cell Line Transformed MESH: Mice ras microarry Cell Line Transformed Oligonucleotide Array Sequence Analysis [SDV.MHEP.EM] Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism Expressed Sequence Tags MEF MESH: Oligonucleotide Array Sequen Gene Expression Profiling Research MESH: Embryo E1A MESH: Gene Expression Regulation Neoplastic [SDV.MHEP.EM]Life Sciences [q-bio]/Human health and pathology/Endocrinology and metabolism Fibroblasts lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens Embryo Mammalian MESH: Adenovirus E1A Proteins Up-Regulation Gene Expression Regulation Neoplastic Cell Transformation Neoplastic MESH: Cell Transformation Neoplastic MESH: Fibroblasts gene expression [SDV.BBM.GTP] Life Sciences [q-bio]/Biochemistry Molecular Biology/Genomics [q-bio.GN] Adenovirus E1A Proteins |
| Zdroj: | Molecular Cancer Molecular cancer [electronic resource] Molecular cancer [electronic resource], 2003, 2, pp.19 Molecular Cancer, Vol 2, Iss 1, p 19 (2003) |
| ISSN: | 1476-4598 |
| Popis: | Background Ras is an area of intensive biochemical and genetic studies and characterizing downstream components that relay ras-induced signals is clearly important. We used a systematic approach, based on DNA microarray technology to establish a first catalog of genes whose expression is altered by ras and, as such, potentially involved in the regulation of cell growth and transformation. Results We used DNA microarrays to analyze gene expression profiles of rasV12/E1A-transformed mouse embryonic fibroblasts. Among the ~12,000 genes and ESTs analyzed, 815 showed altered expression in rasV12/E1A-transformed fibroblasts, compared to control fibroblasts, of which 203 corresponded to ESTs. Among known genes, 202 were up-regulated and 410 were down-regulated. About one half of genes encoding transcription factors, signaling proteins, membrane proteins, channels or apoptosis-related proteins was up-regulated whereas the other half was down-regulated. Interestingly, most of the genes encoding structural proteins, secretory proteins, receptors, extracellular matrix components, and cytosolic proteins were down-regulated whereas genes encoding DNA-associated proteins (involved in DNA replication and reparation) and cell growth-related proteins were up-regulated. These data may explain, at least in part, the behavior of transformed cells in that down-regulation of structural proteins, extracellular matrix components, secretory proteins and receptors is consistent with reversion of the phenotype of transformed cells towards a less differentiated phenotype, and up-regulation of cell growth-related proteins and DNA-associated proteins is consistent with their accelerated growth. Yet, we also found very unexpected results. For example, proteases and inhibitors of proteases as well as all 8 angiogenic factors present on the array were down-regulated in transformed fibroblasts although they are generally up-regulated in cancers. This observation suggests that, in human cancers, proteases, protease inhibitors and angiogenic factors could be regulated through a mechanism disconnected from ras activation. Conclusions This study established a first catalog of genes whose expression is altered upon fibroblast transformation by rasV12/E1A. This catalog is representative of the genome but not exhaustive, because only one third of expressed genes was examined. In addition, contribution to ras signaling of post-transcriptional and post-translational modifications was not addressed. Yet, the information gathered should be quite useful to future investigations on the molecular mechanisms of oncogenic transformation. |
| Databáze: | OpenAIRE |
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