The control of epithelial cell proliferation, differentiation, and apoptosis requires a balance between signaling and transcriptional regulation. Recent developments in pancreatic cell research have revealed that transforming growth factor-β (TGF-β) signaling is important for the regulation of each of these phenomena. More importantly, perturbations in this pathway are associated with pancreatic cancer. A chief example of these alterations is the mutation in the TGF-β-regulated transcription factor Smad4/DPC4 that is found in a large percentage of pancreatic tumors. Surprisingly, studies on transcription factors have remained an underrepresented area of pancreatic research. However, the discovery of Smad4/DPC4 as a transcription factor fueled further studies aimed at characterizing transcription factors involved in normal and neoplastic pancreatic cell growth. Our laboratory recently described the existence of a novel family of zinc finger transcription factors, TGF-β-inducible early-response gene (TIEG)1 and TIEG2, from the exocrine pancreas that, similarly to Smads, participate in the TGF-β response and inhibit epithelial cell proliferation. This review therefore focuses on describing the structure and function of these two families of transcription factor proteins that are becoming key players in the regulation of pancreatic cell growth.
Transforming growth factor-β inhibition of epithelial cell proliferation linked to the expression of a 53-kDa membrane receptor
