The Ras signaling pathway in mammary tumorigenesis and metastasis

The Ras superfamily of GTPases act as important regulatory switches to co-o rdinate extracellular stimuli with activation of intracellular signaling pa thways and appropriate biological responses. The Ras branch of this superfa mily includes H-, K- and N-Ras, which are commonly mutated in particular hu man cancers, but notably not in those of the breast. Instead, in breast can cer the signaling pathways involving these GTPases may be upregulated due t o increased coupling to growth factor receptors or other tyrosine kinases c ommonly overexpressed in this disease, or increased expression of regulator s, the Ras protein itself, or downstream effecters. Functional studies util izing both in vitro and in vivo models demonstrate that Ras signaling can r egulate a variety of endpoints relevant to breast cancer progression, inclu ding anchorage dependent and independent growth, tumorigenesis, steroid sen sitivity and invasion. Finally, analysis of the processing and signaling me chanisms of the Ras superfamily has identified potential targets for therap eutic intervention.