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首页> 外文期刊>Journal of Medical Virology >Activities of human papillomavirus 16 E6 natural variants in human keratinocytes.
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Activities of human papillomavirus 16 E6 natural variants in human keratinocytes.

机译：人角化细胞中人乳头瘤病毒16 E6自然变异的活性。

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摘要

Genetic variations in the E6 oncogene have been associated with different risk for cancer progression. In the present study, the functional significance of human papillomavirus (HPV) polymorphism in the E6 oncogene was investigated. Ten HPV16 E6 variants containing amino acid substitutions in the N-terminal region of E6 were evaluated for different biological and biochemical activities in human keratinocytes, the target cells for HPV infection. Western blot analyses of primary foreskin human keratinocytes or immortalized human keratinocytes, stably transduced with the E6 variants, revealed reduced p53 and Bax levels in all E6 expressing cultures. The reduction induced by most E6 proteins was at similar levels and comparable to the reduction induced by the E6 prototype. The ability of the proteins to induce serum/calcium-differentiation resistant colonies in primary keratinocytes was more variable. Overall activities of the variants ranged between 0.24- and 2.18-fold of the E6 prototype activity. The I27R/L83V variant showed the lowest activity whereas the R8Q variant showed the highest activity. The L83V polymorphism previously associated with risk for cancer progression in some populations, showed significant activity, comparable to that of the E6 prototype, in reducing p53 and Bax levels. Furthermore, this variant showed enhancement in the ability to induce colonies resistant to serum/calcium-triggered differentiation, however, the difference from the prototype was not statistically significant. This, and augmentation of other described functions might result in differences in L83V pathogenicity.
机译：E6癌基因的遗传变异与癌症进展的不同风险相关。在本研究中，研究了人类乳头瘤病毒（HPV）多态性在E6癌基因中的功能意义。评估了在E6 N端区域含有氨基酸取代的10个HPV16 E6变体在人角质形成细胞（HPV感染的靶细胞）中具有不同的生物和生化活性。用E6变体稳定转导的原包皮人角质形成细胞或永生化人角质形成细胞的蛋白质印迹分析显示，在所有表达E6的培养物中p53和Bax水平降低。大多数E6蛋白诱导的还原与E6原型诱导的还原处于相似的水平，并且相当。蛋白质在原代角质形成细胞中诱导血清/钙分化抗性集落的能力变化更大。这些变体的总体活性是E6原型活性的0.24到2.18倍。 I27R / L83V变体显示最低活性，而R8Q变体显示最高活性。先前与某些人群的癌症发展风险相关的L83V多态性在降低p53和Bax水平方面表现出与E6原型相当的显着活性。此外，该变体显示出诱导对血清/钙触发的分化具有抗性的菌落的能力增强，但是，与原型的差异在统计学上不显着。这以及其他描述功能的增强可能会导致L83V致病性的差异。

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