TGF-β induces telomerase-dependent pancreatic tumor cell cycle arrest

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