title: A low threshold level of expression of mutant-template telomerase RNA inhibits human tumor cell proliferation.
abstract: 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.
authors: Department of Biochemistry and Biophysics, University of California, San Francisco, CA 94143-0448, USA.
authors: M M
authors: MM
authors: Kim
authors: M A
authors: MA
authors: Rivera
authors: I L
authors: IL
authors: Botchkina
authors: R
authors: R
authors: Shalaby
authors: A D
authors: AD
authors: Thor
authors: E H
authors: EH
authors: Blackburn
mesh_terms: D002455:Cell Division / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D009369:Neoplasms / Q000235:genetics* / Q000473:pathology*; D012313:RNA / Q000235:genetics*; D019098:Telomerase / Q000235:genetics*; D013698:Templates, Genetic; D014407:Tumor Cells, Cultured
chemical_list: D012313:RNA; D019098:Telomerase