KIPS OFF TO MYC - IMPLICATIONS FOR TGF-BETA SIGNALING

Loss of sensitivity to the negative growth regulator transforming grow th factor beta (TGF beta) is a feature of many different tumor types a nd is likely involved in tumor progression. In some cases this loss of sensitivity to TGF beta has been shown to be manifest in the absence of membrane-associated TGF beta receptor complexes, thus preventing in itiation of antiproliferative signals from the cell surface. In others , loss of sensitivity to TGF beta-induced inhibitory signals has been attributed to loss of function of intracellular effecters of TGF beta- induced inhibitory signals due to mutation or allelic loss of effector genes and their products. The intracellular effecters of TGF beta inh ibitory signals have been shown to be involved in the normal regulatio n of progression through the cell cycle, specifically during G(1) phas e. In this manner, elucidation of the mechanisms by which TGF beta inh ibits cell growth not only helps us identify steps involved in tumor p rogression, but also allows us to better understand how cells regulate progression through the cell cycle. (C) 1997 Wiley-Liss, Inc.