Oncogenic signaling pathways and deregulated target genes.

A limited number of somatic mutations are known to trigger malignancy via chronic activation of cellular signaling pathways. High-throughput analysis of gene expression in cancer cells has revealed a plethora of deregulated genes by far exceeding the number of known genetic alterations. Targeted tumor therapy takes advantage of deregulated signaling in cancer.

Effects of Ras signaling on gene expression analyzed by customized microarrays.

Many signal transduction processes converge on Ras proteins that serve as molecular switches to couple external stimuli with cytoplasmic and nuclear targets. Oncogenic mutations lock Ras proteins in their activated state. Cellular responses to permanent Ras activation such as the induction of neoplastic phenotypes are mediated by distinct transcriptional alterations.

Transcriptional basis of KRAS oncogene-mediated cellular transformation in ovarian epithelial cells.

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.