The E6 and E7 proteins of the cutaneous human papillomavirus type 38 display transforming properties
The E6 and E7 proteins of the cutaneous human papillomavirus type 38 display transforming properties
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DOI：
10.1128/jvi.77.3.2195-2206.2003
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发表时间：
2003-02-01
影响因子：
5.4
通讯作者：
Tommasino, M
中科院分区：
文献类型：
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作者：
Caldeira, S;Zehbe, I;Tommasino, M
几项研究表明，皮肤人乳头瘤病毒（hpv）参与非黑色素瘤皮肤癌的发展。在这里，我们表征了三种皮肤HPV型，10,20和38的E7蛋白的体外特性，这三种类型在皮肤标本中经常检测到。我们发现HPV38 E7能够使肿瘤抑制因子pRb失活，并诱导G(1)/S过渡控制的丧失，这是致癌过程中的一个关键事件。相比之下，HPV10和hpv20e7蛋白在体外不显示这些转化活性。我们还发现HPV38的两种早期蛋白E6和E7足以破坏原代细胞的细胞周期和衰老程序，诱导原代人角质形成细胞（天然宿主细胞）活跃和持久的增殖。我们的研究表明，这种皮肤型HPV的E6和E7在人原代细胞中具有转化活性，提示HPV38感染在皮肤癌变中起作用。为了进一步支持这种作用，我们在大约50%的非黑色素瘤皮肤癌中检测到HPV38 DNA，但仅在10%的健康皮肤样本中检测到（P < 0.001）。
Several studies have suggested the involvement of cutaneous human papillomaviruses (HPVs) in the development of nonmelanoma skin cancers. Here we have characterized the in vitro properties of E7 proteins of three cutaneous HPV types, 10, 20, and 38, which are frequently detected in skin specimens. We show that HPV38 E7 is able to inactivate the tumor suppressor pRb and induces loss of G(1)/S transition control, a key event in carcinogenesis. In contrast, HPV10 and HPV20 E7 proteins do not display these in vitro transforming activities. We also show that the two early proteins E6 and E7 of HPV38 are sufficient to corrupt the cell cycle and senescence programs in primary cells, inducing active and long-lasting proliferation of primary human keratinocytes, the natural host cells. Our study shows that E6 and E7 of this cutaneous HPV type have transforming activity in primary human cells, suggesting a role for HPV38 infection in skin carcinogenesis. In further support of such a role, we detected HPV38 DNA in approximately 50% of nonmelanoma skin cancers, but only in 10% of healthy skin specimens (P < 0.001).