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Bone Morphogenetic Protein-7 Inhibits Telomerase Activity, Telomere Maintenance, and Cervical Tumor Growth

Department of Immunology, Central Eastern Clinical School, Monash University, Melbourne, Australia

Requests for reprints: Jun-Ping Liu or He Li, Department of Immunology, Central Eastern Clinical School, Alfred Medical Research and Education Precinct, Commercial Road, Prahran, Victoria 3181, Australia. Phone: 61-3-99030715; Fax: 61-3-99030120; E-mail: jun-ping.liu{at}med.monash.edu.au or he.li{at}med.monash.edu.au.

Key Words: BMP7 • telomerase • telomeres • tumor growth inhibition • cervical cancer

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. [Cancer Res 2008;68(22):9157–66]