A Low Threshold Level of Expression of Mutant-Template Telomerase RNA Inhibits Human Tumor Cell Proliferation

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 98; no. 14; pp. 7982 - 7987
• Main Authors: Kim, Moses M., Rivera, Melissa A., Botchkina, Inna L., Shalaby, Refaat, Thor, Ann D., Blackburn, Elizabeth H.
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 03-07-2001; National Acad Sciences; The National Academy of Sciences
• Series: From the Cover
• Subjects: Apoptosis; Biological Sciences; Breast cancer; Cell cycle; Cell Division - genetics; Cell growth; Cell lines; Data lines; DNA; Gene Expression Regulation, Neoplastic; Humans; Medical research; Mutation; Neoplasms - genetics; Neoplasms - pathology; Prostate cancer; Ribonucleic acid; RNA; RNA - genetics; Telomerase - genetics; Telomeres; Templates, Genetic; Tumor cell line; Tumor Cells, Cultured; Tumors
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.131211098

The ribonucleoprotein telomerase synthesizes telomeric DNA by copying an intrinsic RNA template. In most cancer cells, telomerase is highly activated. Here we report a telomerase-based antitumor strategy: expression of mutant-template telomerase RNAs in human cancer cells. We expressed mutant-template human telomerase RNAs in prostate (LNCaP) and breast (MCF-7) cancer cell lines. Even a low threshold level of expression of telomerase RNA gene constructs containing various mutant templates, but not the control wild-type template, decreased cellular viability and increased apoptosis. This occurred despite the retention of normal levels of the endogenous wild-type telomerase RNA and endogenous wild-type telomerase activity and unaltered stable telomere lengths. In vivo tumor xenografts of a breast cancer cell line expressing a mutant-template telomerase RNA also had decreased growth rates. Therefore, mutant-template telomerase RNAs exert a strongly dominant-negative effect on cell proliferation and tumor growth. These results support the potential use of mutant-template telomerase RNA expression as an antineoplastic strategy.