TGFβ-mediated signaling and transcriptional regulation in pancreatic development and cancer

Transforming growth factor-beta (TGF beta) plays a critical role in pancreatic development and cell proliferation. Binding of TGF beta to its membrane receptor kinases activates the Smad signaling proteins, allowing them to translocate to the nucleus and participate in the transcriptional control of TGF target genes. In addition, there is an increasing number of cellular mechanisms affecting the final response of a cell to TGF beta. This includes crosstalk with other signaling pathways and the induction of TGF beta early response genes, such as the TGF beta -inducible early response gene (TIEG) family of transcription factors. Like the Smads, TIEGs behave as downstream effector proteins in TGF beta -mediated pancreatic growth control. The discovery of the Smads and TIEGs has provided new insights into TGF beta -regulated functions. Their significance in pancreatic development and cancer is discussed in this review. Curr Opin Gastroenterol 2001, 17:434-440 (C) 2001 Lippincott Williams & Wilkins, Inc.