Integrated transcriptome analysis of the cellular mechanisms associated with Ha-ras-dependent malignant transformation of the human breast epithelial MCF7 cell line
| Autor: | Céline Pillot‐Brochet, Aurélie Le Cam, Sarah Wagner, Laurent Buffat, François Iris, Sophie Malinge, Michel Crepin, Christophe Bozic, Franck Gadal |
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| Přispěvatelé: | Physiopathologie et pharmacologie cellulaires et moléculaires, Université de Nantes (UN)-IFR26-Institut National de la Santé et de la Recherche Médicale (INSERM), Valigen |
| Jazyk: | angličtina |
| Rok vydání: | 2003 |
| Předmět: |
Transcription
Genetic Breast Neoplasms Biology Oncogene Protein p21(ras) Malignant transformation Transcriptome 03 medical and health sciences 0302 clinical medicine Genetics Tumor Cells Cultured Humans Breast 030304 developmental biology Cell Line Transformed Oligonucleotide Array Sequence Analysis 0303 health sciences Cell Death Cell growth Gene Expression Profiling Computational Biology Nucleic Acid Hybridization Reproducibility of Results Epithelial Cells Articles Models Theoretical Cell biology Gene expression profiling Gene Expression Regulation Neoplastic Cell Transformation Neoplastic Tumor progression Suppression subtractive hybridization 030220 oncology & carcinogenesis Female Signal transduction [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology Algorithms |
| Zdroj: | Nucleic Acids Research Nucleic Acids Research, Oxford University Press, 2003, 31 (19), pp.5789-5804. ⟨10.1093/nar/gkg762⟩ |
| ISSN: | 0305-1048 1362-4962 |
| DOI: | 10.1093/nar/gkg762⟩ |
| Popis: | To understand the cellular mechanisms of malignant transformation induced by constitutive activation of the ras oncogene (Ha-ras), we used a subtractive hybridization method (VGID™) together with an integrative analytical procedure based upon literature databases in the form of extensive interaction graphs. We found 166 over- and under-expressed genes which, in the human MCF7-ras breast epithelial cell line, are involved in the different aspects of tumoral transformation such as defined signaling pathways, cellular growth, protection against apoptosis, extracellular matrix and cytoskeleton remodeling. Integrative analysis led to the construction of a physiological model defining cross-talk and signaling pathway alterations which explicitly suggested mechanisms directly involved in tumor progression. The model further suggested points and means of intervention which could induce cell death in Ha-ras-transformed cells specifically. These hypotheses were directly tested in vitro and found to be largely correct, hence indicating that these new analytical and technological approaches allow the discovery of pathology-associated cellular mechanisms and physiologically defined targets leading to phenotype-specific pharmacological interventions. |
| Databáze: | OpenAIRE |
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