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Genetic Analysis of Myc and Telomerase Interactions In Vivo

机译：体内Myc和端粒酶相互作用的遗传分析

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Myc is a transcription factor with pleiotropic effects on tumorigenesis which are likely to be mediated by its target genes. A known Myc transcriptional target is the catalytic subunit of telomerase, Tert. However, the contribution of Tert activation to Myc-induced tumorigenesis in vivo remains unknown. In this study, we addressed the role of telomerase in Myc-induced skin papillomatosis by using compound mice with a switchable Myc gene, Inv-MycERTAM mice, in combination with either telomerase deficiency (Terc?/?) or telomerase overexpression (K5-mTert) in the skin. We first demonstrated that Myc activates telomerase in the skin. With Inv-MycERTAM × Terc?/? mice, we further showed that this telomerase activation is partially required to elicit a full hyperplastic Myc-induced response. The presence of critically short telomeres in late-generation Inv-MycERTAM × Terc?/? mice further reduced the skin lesion induced by Myc. On the other hand, telomerase overexpression in the skin of K5-mTert mice augments Myc-induced hyperplasia in the absence of changes in telomere length, suggesting a direct role of telomerase in the Myc protumorigenic response. Taken together, these results highlight telomerase as a mediator of Myc-induced papillomatosis and suggest telomerase as a putative therapeutic target for Myc-dependent lesions.
机译：Myc是对肿瘤发生具有多效性的转录因子，可能由其靶基因介导。已知的Myc转录靶标是端粒酶Tert的催化亚基。然而，Tert激活体内Myc诱导的肿瘤发生的贡献仍然未知。在这项研究中，我们通过使用具有可转换Myc基因的复合小鼠Inv-MycER TAM 小鼠与端粒酶缺乏症（Terc 结合）解决端粒酶在Myc诱导的皮肤乳头状瘤病中的作用。 ？/？）或皮肤中的端粒酶过度表达（K5-mTert）。我们首先证明Myc激活皮肤中的端粒酶。对于Inv-MycER TAM ×Terc ？/？小鼠，我们进一步表明，端粒酶激活是引起完全增生性Myc诱导的反应的部分原因。晚期Inv-MycER TAM ×Terc ？/？小鼠存在严重短的端粒，进一步减轻了Myc诱导的皮肤损伤。另一方面，在端粒长度没有变化的情况下，K5-mTert小鼠皮肤中的端粒酶过度表达会增加Myc诱导的增生，提示端粒酶在Myc致瘤反应中具有直接作用。综上所述，这些结果突出了端粒酶作为Myc诱导的乳头状瘤病的介体，并暗示端粒酶是Myc依赖性病变的假定治疗靶标。

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