Glucocorticoids stimulate growth of human papillomavirus type 16 (HPV16)-immortalized human keratinocytes and support HPV16-mediated immortalization without affecting the levels of HPV16 E6/E7 mRNA
Glucocorticoids stimulate growth of human papillomavirus type 16 (HPV16)-immortalized human keratinocytes and support HPV16-mediated immortalization without affecting the levels of HPV16 E6/E7 mRNA
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DOI：
10.1006/excr.1997.3729
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发表时间：
1997-10-10
影响因子：
3.7
通讯作者：
Pirisi, L
中科院分区：
文献类型：
--
作者：
Khan, MA;Canhoto, AJ;Pirisi, L
我们研究了糖皮质激素氢化可的松和地塞米松对人乳头瘤病毒16型（HPV 16）介导的人细胞癌变的影响，使用正常人角质形成细胞（HKc）和通过转染HPV 16 DNA永生化的HKc（HKc/HPV 16）。正常HKc增殖不需要糖皮质激素。相比之下，生长的早期通道HKc/HPV 16严格需要这些激素，虽然糖皮质激素的依赖性变得不那么严格，在体外的进展。HPV 16 DNA永生化后，HKc早期获得了糖皮质激素依赖性，高效的HKc永生化需要糖皮质激素。然而，用氢化可的松或地塞米松处理HKc/HPV 16并不增加HPV 16 E6/E7 mRNA或蛋白的稳态水平。在HPV 16上游调控区和P97启动子的控制下表达的萤火虫荧光素酶活性在地塞米松处理HeLa后增加约4倍，但在HKc/HPV 16中仅增加2倍，在SiHa中增加不到2倍。然而，所有这些细胞系表达足够的内源性糖皮质激素受体，以允许小鼠乳腺肿瘤病毒启动子的地塞米松反应。这些结果表明，除了糖皮质激素对HPV 16早期基因表达的直接影响外，其他机制可能有助于这些类固醇对HPV 16介导的人类细胞癌变的显著生物学效应。(C)1997年学术出版社。
We investigated the effects of the glucocorticoids hydrocortisone and dexamethasone on human papillomavirus type 16 (HPV16)-mediated human cell carcinogenesis using normal human keratinocytes (HKc) and HKc immortalized by transfection with HPV16 DNA (HKc/HPV16). Normal HKc did not require glucocorticoids for proliferation. In contrast, growth of early passage HKc/HPV16 strictly required these hormones, although glucocorticoid dependence became less stringent during in, vitro progression. Glucocorticoid dependence was acquired by HKc early after immortalization with HPV16 DNA, and glucocorticoids were required for efficient HKc immortalization. However, treatment of HKc/HPV16 with hydrocortisone or dexamethasone did not increase the steady-state levels of HPV16 E6/E7 mRNA or protein. Firefly luciferase activity expressed under the control of the HPV16 upstream regulatory region and P97 promoter increased by about fourfold following dexamethasone treatment of HeLa, but only twofold in HKc/HPV16, and less than twofold in SiHa. However, all of these cell lines expressed sufficient endogenous glucocorticoid receptors to allow for a dexamethasone response of the mouse mammary tumor virus promoter. These results indicate that mechanisms other than a direct influence by glucocorticoids on HPV16 early gene expression may contribute to the striking biological effects of these steroids on HPV16-mediated human cell carcinogenesis. (C) 1997 Academic Press.