宫颈癌是女性生殖道中最常见的恶性肿瘤，与子宫颈持续感染高危型人类乳头瘤病毒（HPV）有关。两种HPV致癌蛋白E6和E7共同使宫颈细胞不衰老，但单独不足以诱导肿瘤形成。在HPV相关的宫颈不典型增生向癌变的过程中，细胞中的TERT基因被激活，TERC基因被扩增。我们质疑这些端粒酶组分的增加是否介导了肿瘤致瘤表型。因此，我们将TERT和TERC基因转导到依赖贴壁、非肿瘤性的E6/E7角化细胞中。结果表明，这些细胞产生了显著的表皮间质转化（EMT）形态学变化，以及相关的Vimentin、N-cadherin、ZEB1、SNAIL和MMP2表达增加，角蛋白和E-cadherin减少。更重要的是，转导的细胞现在不依赖贴壁而且在免疫缺陷小鼠中形成肿瘤。我们的发现表明，在HPV不衰老细胞中过表达端粒酶全酶足够诱导完全的转型表型。本文章受版权保护，未经授权禁止转载。

Cervical cancer is the most frequent malignancy of the female genital tract and is associated with persistent infection of the uterine cervix with high-risk human papillomaviruses (HPV). The two HPV oncoproteins, E6 and E7, cooperatively immortalize cervical cells and are essential but insufficient for inducing tumorigenicity. During the progression of HPV-associated cervical dysplasia to carcinoma, the cellular TERT gene is activated and the TERC gene amplified. We questioned whether these increases in telomerase components might mediate the acquisition of the tumorigenic phenotype. We therefore transduced the TERT and TERC genes into E6/E7 immortalized keratinocytes that were anchorage-dependent and non-tumorigenic. The resultant cells showed a profound morphological change characteristic of epithelial-mesenchymal transition (EMT) as well as a corresponding increase in expression of vimentin, N-cadherin, ZEB1, SNAIL and MMP2 and decrease in keratin and E-cadherin. More important, the transduced cells were now anchorage-independent and formed tumors in immunodeficient mice. Our findings indicate that overexpression of the telomerase holoenzyme in HPV-immortalized cells is sufficient to induce the complete transformed phenotype. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.