Effects of human papillomavirus (HPV) type 16 oncoproteins on the expression of involucrin in human keratinocytes.
Effects of human papillomavirus (HPV) type 16 oncoproteins on the expression of involucrin in human keratinocytes.
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DOI：
10.1186/1743-422x-9-36
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发表时间：
2012-02-14
期刊：
影响因子：
4.8
通讯作者：
Veress G
中科院分区：
文献类型：
--
作者：
Gyöngyösi E;Szalmás A;Ferenczi A;Kónya J;Gergely L;Veress G
人乳头瘤病毒（HPV）的生命周期与角质形成细胞分化密切相关。致癌性HPV感染已被证明会阻碍角质形成细胞的正常分化;然而，导致这种现象的潜在机制尚未阐明。在这里，我们的目的是研究HPV 16 E6和E7癌基因对外皮蛋白（IVL），角质形成细胞分化的一个既定的标志物，在人包皮角质形成细胞（HFK）细胞的表达的影响。血清和高钙诱导HFK细胞分化后，IVL的mRNA和蛋白水平均显著升高。HPV 16的E6和E7癌蛋白共同引起HFK细胞增殖和分化中IVL mRNA和蛋白的强烈下调。为了研究HPV癌基因对IVL启动子的影响，我们进行了瞬时转染试验和荧光素酶试验，发现HPV 16 E6而不是E7抑制增殖HFK细胞中IVL启动子的活性。HPV 16 E6对人IVL启动子的抑制作用可定位于该基因的近端调控区（PRR）。这些结果表明，下调IVL启动子活性的HPV 16 E6显着有助于抑制内源性IVL表达的HPV 16癌蛋白。相反，HPV 16 E7下调内源性IVL表达可能不是由E7对IVL启动子的直接和特异性作用引起的。
The human papillomavirus (HPV) life cycle is closely linked to keratinocyte differentiation. Oncogenic HPV infection has been shown to hamper the normal differentiation of keratinocytes; however, the underlying mechanisms responsible for this phenomenon are yet to be clarified. Here, we aimed to study the effects of HPV16 E6 and E7 oncogenes on the expression of involucrin (IVL), an established marker of keratinocyte differentiation, in human foreskin keratinocyte (HFK) cells. The differentiation of HFK cells by serum and high calcium significantly increased both the mRNA and the protein levels of IVL. The E6 and E7 oncoproteins of HPV16 together caused strong down-regulation of IVL mRNA and protein both in proliferating and in differentiating HFK cells. To study the effects of HPV oncogenes on the IVL promoter, we made transient transfection assays and luciferase tests and found that HPV 16 E6 but not E7 repressed IVL promoter activity in proliferating HFK cells. The inhibitory effect of HPV 16 E6 on the human IVL promoter could be localised to the proximal regulatory region (PRR) of the gene. These results suggest that the down-regulation of IVL promoter activity by HPV 16 E6 significantly contribute to the inhibition of endogenous IVL expression by the HPV 16 oncoproteins. In contrast, the down-regulation of endogenous IVL expression by HPV16 E7 is probably not caused by a direct and specific effect of E7 on the IVL promoter.