Regulation of growth and gene expression in human papillomavirus-transformed keratinocytes by transforming growth factor-beta: implications for the control of papillomavirus infection.
Regulation of growth and gene expression in human papillomavirus-transformed keratinocytes by transforming growth factor-beta: implications for the control of papillomavirus infection.
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通过转化生长因子-β调节人乳头瘤病毒转化的角质形成细胞的生长和基因表达：对控制乳头瘤病毒感染的影响。
DOI：
10.1002/mc.2940060205
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发表时间：
1992
影响因子：
4.6
通讯作者：
Robinson,M
中科院分区：
文献类型：
--
作者：
Braun,L;Dürst,M;Mikumo,R;Crowley,A;Robinson,M
宫颈癌的发生是一个多步骤的过程，似乎是由宫颈鳞状上皮细胞感染有限数量的人乳头瘤病毒（HPV）类型之一引起的。然而，HPV诱导的良性病变向恶性病变演变的机制尚未完全阐明。转化生长因子- β (TGF - β)是一种由皮肤细胞产生的多功能生长因子，在体外抑制包皮和宫颈角化细胞的增殖。我们检测了TGF - β对两种与宫颈癌相关的HPV永生化细胞系生长和病毒早期基因表达的影响，以及TGF - β 1mrna转录物在体内和体外正常细胞和HPV阳性细胞中的表达。我们发现正常细胞和HPV阳性细胞表达相似水平的TGF - β1 mrna，并且在单层和修饰的器官型培养中对三种TGF - β亚型表现出相似的反应模式。特别有趣的是，我们发现HPV16和HPV18的E6和E7早期病毒转化区的表达都被TGF‐β可逆地快速抑制。在详细研究的HPV16阳性细胞系中，抑制HPV表达需要蛋白质合成，并发生在转录水平上。对体外分化信号产生抗性的HPV永生化细胞对TGF - β介导的生长抑制仍然敏感。这些结果表明，HPV转化细胞的生长和病毒基因表达都对TGF - β有反应，提示鳞状上皮中不同细胞类型产生的内源性生长因子可能在宫颈肿瘤的进展中起作用。©1992 Wiley‐Liss, Inc。
Cervical carcinogenesis is a multistep process that appears to be initiated by infection of squamous epithelial cells in the cervix with one of a limited number of human papillomavirus (HPV) types. However, the mechanisms involved in the evolution of benign, HPV‐induced lesions to malignancy have not yet been fully elucidated. Transforming growth factor‐β (TGF‐β), a multifunctional growth factor produced by cells in the skin, inhibits the proliferation of foreskin and cervical keratinocytes in vitro. We examined the effects of TGF‐β on growth and virus early‐gene expression in cell lines immortalized by two HPV types associated with cervical carcinogenesis as well as the expression of TGF‐β1 mRNA transcripts in normal and HPV‐positive cells in vivo and in vitro. We found that normal and HPV‐positive cells expressed similar levels of TGF‐β1 mRNAs and exhibited similar patterns of responsiveness to three isoforms of TGF‐β in both monolayer and modified organotypic cultures. Of particular interest is our finding that the expression of the E6 and E7 early viral transforming regions of both HPV16 and HPV18 was reversibly and rapidly inhibited by TGF‐β. In one HPV16‐positive cell line examined in detail, inhibition of HPV expression required protein synthesis and occurred at the level of transcription. HPV‐immortalized cells selected for resistance to in vitro differentiation signals remained sensitive to TGF‐β‐mediated growth inhibition. These results, showing that both growth and virus gene expression in HPV‐transformed cells were responsive to TGF‐β, suggest that endogenous growth factors produced by different cell types in squamous epithelium may play a role in the progression of cervical neoplasia. © 1992 Wiley‐Liss, Inc.