Activin inhibits telomerase activity in cancer.
Activin is a pleiotropic cytokine with broad tissue distributions. Recent studies demonstrate that activin-A inhibits cancer cell proliferation with unknown mechanisms. In this report, we demonstrate that recombinant activin-A induces telomerase inhibition in cancer cells. In breast and cervical cancer cells, activin-A resulted in telomerase activity in a concentration-dependent manner. Significant inhibition was observed at 10 ng/ml of activin-A, with a near complete inhibition at 80 ng/ml. Consistently, activin-A induced repression of the telomerase reverse transcriptase (hTERT) gene, with the hTERT gene to be suppressed by 60-80% within 24h. In addition, activin-A induced a concomitant increase in Smad3 signaling and decrease of the hTERT gene promoter activity in a concentration-dependent fashion. These data suggest that activin-A triggered telomerase inhibition by down-regulating hTERT gene expression is involved in activin-A-induced inhibition of cancer cell proliferation.
Katik
Indzi
I
Department of Immunology, Monash University, Central Clinical School, Commercial Road, Melbourne, Vic. 3004, Australia.
Mackenzie-Kludas
Charley
C
Nicholls
Craig
C
Jiang
Fang-Xu
FX
Zhou
Shufeng
S
Li
He
H
Liu
Jun-Ping
JP
D028341:Activins / Q000494:pharmacology*; D015536:Down-Regulation; D006367:HeLa Cells; D006801:Humans; D009369:Neoplasms / Q000201:enzymology*; D011994:Recombinant Proteins / Q000494:pharmacology; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000494:pharmacology*
D011994:Recombinant Proteins; D025521:Tumor Suppressor Proteins; C422405:activin A; D028341:Activins; D019098:Telomerase