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Transcriptional basis of KRAS oncogene-mediated cellular transformation in ovarian epithelial cells.
- Source :
- Oncogene; 6/3/2004, Vol. 23 Issue 26, p4536-4555, 20p
- Publication Year :
- 2004
-
Abstract
- To understand the relationship between oncogenic signaling and the reprogramming of gene expression, we performed transcriptional profiling in rat ovarian surface epithelial cells (ROSE), in which neoplastic transformation is driven by a mutated KRAS oncogene. We identified >200 genes whose expression was elevated or reduced following permanent KRAS expression. Deregulated KRAS-responsive genes encode transcriptional regulators, signaling effectors, proteases, extracellular matrix and adhesion proteins, transformation-suppressing proteins and negative growth regulators. Many of them have not been previously identified in cells expressing oncogenic RAS genes or in other well-studied models of oncogenic signaling. The number of critical genes related to the execution of anchorage-independent proliferation and epithelial-mesenchymal transition was narrowed down to 79 by selectively inhibiting the mitogen-activated protein kinase (MAPK/ERK) and phosphatidylinositol 3-kinase (PI3K) pathways. Blocking MAPK/ERK-signaling caused reversion to the normal epithelial phenotype in conjunction with the reversal of deregulated target transcription to pretransformation levels. In addition, silencing of the overexpressed transcriptional regulator Fra-1 by RNA interference resulted in growth reduction, suggesting that this factor partially contributes to, but is not sufficient for the proliferative capacity of KRAS-transformed epithelial cells.Oncogene (2004) 23, 4536-4555. doi:10.1038/sj.onc.1207585 Published online 5 April 2004 [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 09509232
- Volume :
- 23
- Issue :
- 26
- Database :
- Complementary Index
- Journal :
- Oncogene
- Publication Type :
- Academic Journal
- Accession number :
- 13296956
- Full Text :
- https://doi.org/10.1038/sj.onc.1207585