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Gonzalez-Suarez EES, Ramirez A, Flores JM, Martin-Caballero J, Jorcano JL, Blasco MAIncreased epidermal tumors and increased skin wound healing in transgenic mice overexpressing the catalytic subunit of telomerase, mTERT, in basal keratinocytes. EMBO J 20:2619-2630

Department of Immunology and Oncology, National Centre of Biotechnology, E-28049 Madrid.
The EMBO Journal (Impact Factor: 10.75). 07/2001; 20(11):2619-30. DOI: 10.1093/emboj/20.11.2619
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ABSTRACT Telomerase transgenics are an important tool to assess the role of telomerase in cancer, as well as to evaluate the potential use of telomerase for gene therapy of age-associated diseases. Here, we have targeted the expression of the catalytic component of mouse telomerase, mTERT, to basal keratinocytes using the bovine keratin 5 promoter. These telomerase-transgenic mice are viable and show histologically normal stratified epithelia with high levels of telomerase activity and normal telomere length. Interestingly, the epidermis of these mice is highly responsive to the mitogenic effects of phorbol esters, and it is more susceptible than that of wild-type littermates to the development skin tumors upon chemical carcinogenesis. The epidermis of telomerase-transgenic mice also shows an increased wound-healing rate compared with wild-type littermates. These results suggest that, contrary to the general assumption, telomerase actively promotes proliferation in cells that have sufficiently long telomeres and unravel potential risks of gene therapy for age-associated diseases based on telomerase upregulation.

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Available from: Juana M Flores, Aug 25, 2015
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    • "Next, we used our wild-type mouse aging metabolomic signature to predict the ages of transgenic mice overexpressing the telomerase reverse-transcriptase subunit or TERT in various stratified epithelia (K5-TERT mice). We have previously shown that K5-TERT mice have increased tissue fitness and a delayed aging (Gonzalez-Suarez et al., 2001, 2005). Serum metabolomic profiles were not significantly different when comparing "
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    • "Histopathology was performed as previously described (Gonzá lez-Suá rez et al., 2001). Briefly, tissues and organs were fixed for 24 hr in a 10% neutral buffered formalin solution at room temperature, dehydrated through graded alcohols and xylene, and embedded in paraffin. "
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    • "It is also unclear whether telomerase activity can prevent any type of DNA damage at telomeres as an overexpression of TERT could not suppress irradiation-induced cellular senescence or the persistence of telomeric DDR following irradiation, H 2 O 2 , or chemotherapy induced DNA damage (Hewitt et al, 2012). The data could provide a plausible explanation for the increased tumorigenesis in telomerase transgenic mice—a finding which is difficult to explain by telomere length dependent effects of telomerase given the long telomere reserves in mouse tissues (Gonzalez-Suarez et al, 2001). According to the findings of Suram et al (2012), anti-telomerase therapies could have immediate anti-cancer effects in tumours depending on telomerase-mediated healing of stalled replication forks at telomeres. "
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