Increased epidermal tumors and increased skin wound healing in transgenic mice overexpressing the catalytic subunit of telomerase, mTERT, in basal keratinocytes
Increased epidermal tumors and increased skin wound healing in transgenic mice overexpressing the catalytic subunit of telomerase, mTERT, in basal keratinocytes
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DOI：
10.1093/emboj/20.11.2619
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发表时间：
2001-06-01
期刊：
影响因子：
11.4
通讯作者：
Blasco, MA
中科院分区：
文献类型：
--
作者：
González-Suárez, E;Samper, E;Blasco, MA
端粒酶转基因是评估端粒酶在癌症中的作用以及评估端粒酶在年龄相关疾病基因治疗中的潜在用途的重要工具。在这里，我们使用牛角蛋白 5 启动子将小鼠端粒酶催化成分 mTERT 的表达靶向基底角质形成细胞。这些端粒酶转基因小鼠具有存活能力，并显示出组织学正常的复层上皮，具有高水平的端粒酶活性和正常的端粒长度。有趣的是，这些小鼠的表皮对佛波酯的促有丝分裂作用高度敏感，并且比野生型同窝小鼠更容易在化学致癌作用下形成皮肤肿瘤。与野生型同窝小鼠相比，端粒酶转基因小鼠的表皮也显示出更高的伤口愈合率。这些结果表明，与一般假设相反，端粒酶积极促进具有足够长端粒的细胞的增殖，并揭示了基于端粒酶上调的年龄相关疾病基因治疗的潜在风险。
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.