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首页> 外文期刊>Molecular and Cellular Biology >Recapitulation of the Effects of the Human Papillomavirus Type 16 E7 Oncogene on Mouse Epithelium by Somatic Rb Deletion and Detection of pRb-Independent Effects of E7 In Vivo
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Recapitulation of the Effects of the Human Papillomavirus Type 16 E7 Oncogene on Mouse Epithelium by Somatic Rb Deletion and Detection of pRb-Independent Effects of E7 In Vivo

机译：通过体细胞Rb删除和检测E7的pRb独立效应，概述了人乳头瘤病毒16型E7癌基因对小鼠上皮的影响。

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Although the human papillomavirus (HPV) E7 oncogene is known to contribute to the development of human cervical cancer, the mechanisms of its carcinogenesis are poorly understood. The first identified and most recognized function of E7 is its binding to and inactivation of the retinoblastoma tumor suppressor (pRb), but at least 18 other biological activities have also been reported for E7. Thus, it remains unclear which of these many activities contribute to the oncogenic potential of E7. We used a Cre-lox system to abolish pRb expression in the epidermis of transgenic mice and compared the outcome with the effects of E7 expression in the same tissue at early ages. Mice lacking pRb in epidermis showed epithelial hyperplasia, aberrant DNA synthesis, and improper differentiation. In addition, Rb-deleted epidermis (i.e., epidermis composed of cells with Rb deleted) exhibited centrosomal abnormalities and failed to arrest the cell cycle in response to ionizing radiation. Transgenic mice expressing E7 in skin display the same range of phenotypes. In sum, few differences were detected between Rb-deleted epidermis and E7-expressing epidermis in young mice. However, when both E7 was expressed and Rb was deleted in the same tissue, increased hyperplasia and dysplasia were observed. These findings indicate that inactivation of the Rb pathway can largely account for E7's phenotypes at an early age, but that pRb-independent activities of E7 are detectable in vivo.
机译：尽管已知人乳头瘤病毒（HPV）E7癌基因可促进人宫颈癌的发展，但其致癌机制尚不清楚。 E7的第一个被确认和最公认的功能是它与视网膜母细胞瘤抑癌剂（pRb）结合并使其失活，但也已报道了E7至少有18种其他生物学活性。因此，目前尚不清楚这些许多活动中有哪些会促进E7的致癌潜力。我们使用Cre-lox系统消除了转基因小鼠表皮中pRb的表达，并将结果与​​E7表达在早期相同组织中的作用进行了比较。表皮中缺乏pRb的小鼠表现出上皮增生，异常的DNA合成和不适当的分化。此外，缺失了 Rb 的表皮（即由缺失了 Rb 的细胞组成的表皮）表现出中心体异常，并且不能响应电离辐射而阻止细胞周期。在皮肤中表达E7的转基因小鼠表现出相同的表型范围。总之，在年轻小鼠中，缺失 Rb 的表皮和表达E7的表皮之间几乎没有差异。但是，当在同一组织中同时表达E7和删除 Rb 时，观察到增生和异型增生。这些发现表明，Rb途径的失活在很大程度上可以解释E7的表型，但在体内可检测到E7的pRb独立活性。

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