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.
Department of Immunology, Monash University, Central Clinical School, AMREP, Commercial Road, Melbourne, Victoria 3004, Australia. he.li@med.monash.edu.au
Lucy
L
Cassar
He
H
Li
Fang-Xu
FX
Jiang
Jun-Ping
JP
Liu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000187:drug effects / Q000378:metabolism; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D010190:Pancreatic Neoplasms / Q000201:enzymology* / Q000473:pathology*; D010766:Phosphorylation / Q000187:drug effects; D021381:Protein Transport / Q000187:drug effects; D051381:Rats; D016196:S Phase / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects; D051900:Smad3 Protein / Q000378:metabolism; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000494:pharmacology*
D051900:Smad3 Protein; D016212:Transforming Growth Factor beta; D019098:Telomerase