Akgül Baki, Ghali Lucy, Davies Derek, Pfister Herbert, Leigh Irene M, Storey Alan
Skin Tumour Laboratory, Cancer Research UK, London, UK.
Exp Dermatol. 2007 Jul;16(7):590-9. doi: 10.1111/j.1600-0625.2007.00569.x.
Human papillomaviruses (HPV) have been associated with the development of non-melanoma skin cancer (NMSC) but the molecular mechanisms of the role of the virus in NMSC development are not clearly understood. Abnormal epithelial differentiation seen in malignant transformation of keratinocytes is associated with changes in keratin expression. The purpose of this study was to investigate the phenotype of primary human adult keratinocytes expressing early genes of HPV8 with specific reference to their differentiation and cell cycle profile to determine whether early genes of HPV8 lead to changes that are consistent with transformation. The expression of HPV8 early genes either individually or simultaneously caused distinct changes in the keratinocyte morphology and induced an abnormal keratin expression pattern, that included simple epithelial (K8, K18, K19), hyperproliferation-specific (K6, K16), basal-specific (K14, K15) and differentiation-specific (K1, K10) keratins. Our results indicate that expression of HPV8 early genes disrupts the normal keratin expression pattern in vitro. Expression of HPV8-E7 alone caused polyploidy that was associated with decreased expression of p21 and pRb. Expression of individual genes or in combination differentially influenced cell morphology and cell cycle distribution which might be important in HPV8-induced keratinocyte transformation.
人乳头瘤病毒（HPV）与非黑素瘤皮肤癌（NMSC）的发生有关，但病毒在NMSC发生中作用的分子机制尚不清楚。角质形成细胞恶性转化中出现的异常上皮分化与角蛋白表达的变化有关。本研究的目的是研究表达HPV8早期基因的原代成人人类角质形成细胞的表型，特别关注其分化和细胞周期谱，以确定HPV8早期基因是否导致与转化一致的变化。HPV8早期基因单独或同时表达会导致角质形成细胞形态发生明显变化，并诱导异常的角蛋白表达模式，包括简单上皮角蛋白（K8、K18、K19）、过度增殖特异性角蛋白（K6、K16）、基底特异性角蛋白（K14、K15）和分化特异性角蛋白（K1、K10）。我们的结果表明，HPV8早期基因的表达在体外破坏了正常的角蛋白表达模式。单独表达HPV8-E7会导致多倍体形成，这与p21和pRb表达降低有关。单个基因或组合基因的表达差异影响细胞形态和细胞周期分布，这可能在HPV8诱导的角质形成细胞转化中起重要作用。
