MICROSATELLITE INSTABILITY AND A TGF-BETA RECEPTOR - CLUES TO A GROWTH-CONTROL PATHWAY

Defects of growth inhibitory pathways have an important role in disord ers of cell growth and differentiation. The discovery of a mutation in one of the principle components of the transforming growth factor bet a (TGF beta) receptor system which is linked to a DNA repair defect(1) represents one possible mechanism of escape from negative regulatory influences acting upon cells. TGF beta is a pre-eminent negative growt h factor and this article discusses (1) the role of TGF beta in mainta ining epithelial homeostasis; (2) how breakdown of inhibitory pathways can promote neoplastic development; (3) the significance of a recepto r defect in a negative signalling pathway; and (4) the potential thera peutic sequelae resulting from restoration of cellular responsiveness to IGF beta.