Ras signal transduction in carcinogenesis and progression of bladder cancer: molecular target for treatment?

Abstract.

Ras oncogenes are considered to play a key role in the carcinogenesis and progression of human bladder cancer. The oncogenes code for the Ras p21 proteins, which localize in the internal part of the cell membrane and act as molecular switches to mediate downstream signaling from a variety of extracellular stimuli. Activation of Ras proteins induces the constitutive activation of downstream kinase cascades, which results in continuous mitogenic signaling and transformation of immortalized cells in human bladder cancer. Therefore inactivation of the activated Ras function might be effective for the development of a novel treatment strategy against human bladder cancer. Recently several ways to suppress Ras activities, including inhibitors of Ras signal transduction and a ras suppressor mutant, have been reported. Here we review the current concepts of the basic mechanisms of the intracellular Ras signaling pathway and ras activation in the carcinogenesis and progression of human bladder cancer and discuss clinical potentials of their therapeutic interventions.