TGF-beta induces telomerase-dependent pancreatic tumor cell cycle arrest.

Recent studies suggest that transforming growth factor beta (TGF-beta) inhibits telomerase activity by repression of the telomerase reverse transcriptase (TERT) gene. In this report, we show that TGF-beta induces TERT repression-dependent apoptosis in pancreatic tumor, vascular smooth muscle, and cervical cancer cell cultures. TGF-beta activates Smad3 signaling, induces TERT gene repression and results in G1/S phase cell cycle arrest and apoptosis. TERT over-expression stimulates the G1/S phase transition and alienates TGF-beta-induced cell cycle arrest and apoptosis. Our data suggest that telomere maintenance is a limiting factor of the transition of the cell cycle. TGF-beta triggers cell cycle arrest and death by a mechanism involving telomerase deregulation of telomere maintenance.