The telomerase RNA component Terc is required for the tumour-promoting effects of Tert overexpression.
A role for the telomerase reverse transcriptase subunit (Tert) in tumorigenesis independent of telomere length is emerging. K5-Tert mice, which overexpress Tert in the skin, show increased tumorigenesis and faster wound healing than wild-type controls. Here, we demonstrate that the telomerase RNA component Terc is necessary to mediate these effects of Tert overexpression. In contrast to K5-Tert mice, K5-Tert mice in a Terc-deficient background, K5-Tert/Terc-/-, do not show increased tumorigenesis or increased wound healing compared with wild-type controls. Indeed, K5-Tert/Terc-/- mice show a reduction in tumour growth compared with Terc-/- controls, indicating an inhibitory effect of Tert overexpression in the absence of Terc. These results indicate that the tumour-promoting effects of Tert overexpression require the formation of Tert-Terc complexes. In addition, we show that the increased expression of Tert in the absence of Terc has an inhibitory effect on tumorigenesis, independently of telomere length and telomerase activity. These findings highlight Terc as a target for telomerase-based anticancer therapies.
Cayuela
María Luisa
ML
Molecular Oncology Program, Spanish National Cancer Center (CNIO), 28029 Madrid, Spain.
Flores
Juana M
JM
Blasco
María A
MA
D000818:Animals; D002471:Cell Transformation, Neoplastic / Q000187:drug effects / Q000235:genetics*; D043171:Chromosomal Instability / Q000235:genetics; D002869:Chromosome Aberrations; D004268:DNA-Binding Proteins; D017353:Gene Deletion; D017404:In Situ Hybridization, Fluorescence; D015603:Keratinocytes / Q000378:metabolism; D051379:Mice; D018345:Mice, Knockout; D009154:Mutation / Q000235:genetics; D009369:Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology*; D021122:Protein Subunits / Q000235:genetics / Q000378:metabolism; D012313:RNA / Q000235:genetics / Q000378:metabolism*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D019098:Telomerase / Q000235:genetics* / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology; D014945:Wound Healing
D004268:DNA-Binding Proteins; D021122:Protein Subunits; C422952:telomerase RNA; D012313:RNA; D019098:Telomerase; C509187:Tert protein, mouse; D013755:Tetradecanoylphorbol Acetate
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