Bone morphogenetic protein-7 inhibits telomerase activity, telomere maintenance, and cervical tumor growth.
Telomere maintenance is critical in tumor cell immortalization. Here, we report that the cytokine bone morphogenetic protein-7 (BMP7) inhibits telomerase activity that is required for telomere maintenance in cervical cancer cells. Application of human recombinant BMP7 triggers a repression of the human telomerase reverse transcriptase (hTERT) gene, shortening of telomeres, and hTERT repression-dependent cervical cancer cell death. Continuous treatment of mouse xenograft tumors with BMP7, or silencing the hTERT gene, results in sustained inhibition of telomerase activity, shortening of telomeres, and tumor growth arrest. Overexpression of hTERT lengthens telomeres and blocks BMP7-induced tumor growth arrest. Thus, BMP7 negatively regulates telomere maintenance, inducing cervical tumor growth arrest by a mechanism of inducing hTERT gene repression.
Cassar
Lucy
L
Department of Immunology, Central Eastern Clinical School, Monash University, Melbourne, Australia.
Li
He
H
Pinto
Alexander Ruvantha
AR
Nicholls
Craig
C
Bayne
Sharyn
S
Liu
Jun-Ping
JP
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D055419:Bone Morphogenetic Protein 7 / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006367:HeLa Cells; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D009368:Neoplasm Transplantation; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000235:genetics; D016615:Telomere / Q000187:drug effects*; D014183:Transplantation, Heterologous; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
D055419:Bone Morphogenetic Protein 7; C509186:TERT protein, human; D019098:Telomerase