THE EFFECTS OF ONCOGENIC RAS ON FAS EXPRESSION AND SUSCEPTIBILITY TO FAS-MEDIATED APOPTOSIS

Abstract

Cancer is a disease characterized by unregulated cell accumulation resulting from either an increase in the rate of cell proliferation and/or a decrease in the rate of cell death. Regulation of these two processes is of great importance to the development and progression of cancer. One gene involved in the regulation of normal cell growth and differentiation is ras. Ras proteins alter gene expression by activating multiple downstream signal transduction pathways, resulting in the activation of protein kinases that translocate to the nucleus where they mediate the activation of various transcription factors. Mutations within the ras proto-oncogene generate constitutively active forms of Ras that disrupt normal controls on cellular growth and differentiation, leading to the development of a transformed state. Mutations within the ras proto-oncogene have been identified in 30% of human cancers, including cancers of the lung, colon, and pancreas. Although the effects of mutant ras oncogenes on tumor cell proliferation have been well characterized, little is known about the possible anti-apoptotic effects of mutant ras.