Differential effect of tumor necrosis factor on proliferation of primary human keratinocytes and cell lines containing human papillomavirus types 16 and 18.
Differential effect of tumor necrosis factor on proliferation of primary human keratinocytes and cell lines containing human papillomavirus types 16 and 18.
复制标题
肿瘤坏死因子对原代人角质形成细胞和含有人乳头瘤病毒 16 型和 18 型的细胞系增殖的差异作用。
DOI：
10.1002/mc.2940060103
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发表时间：
1992
影响因子：
4.6
通讯作者：
Schlegel,R
中科院分区：
文献类型：
--
作者：
Villa,LL;Vieira,KB;Pei,XF;Schlegel,R
人乳头瘤病毒(HPV16)和人乳头瘤病毒18型永生化角质形成细胞对转化生长因子-β(TGFR-β)的增殖抑制有部分抵抗作用。为了确定这一发现是否反映了对抑制性细胞因子的普遍抵抗，我们研究了肿瘤坏死因子-α(肿瘤坏死因子-α)对正常和人乳头瘤病毒永生化的人包皮角质形成细胞融合培养的影响。原代和HPV16永生化的角质形成细胞对肿瘤坏死因子α敏感，而HPV18永生化的角质形成细胞(以及被猴病毒40永生化的角质形成细胞)对这种细胞因子的抑制作用具有抵抗力。HPV-18诱导更多耐药表型的能力与其更强大的体外转化活性以及与更具侵袭性的肿瘤明显相关。有趣的是，在正常或HPV-16永生化角质形成细胞中，肿瘤坏死因子诱导的生长抑制状态并没有伴随着c-myc RNA或蛋白表达的减少。这与转化生长因子-β抑制正常细胞中c-myc RNA表达的能力形成鲜明对比。显然，HPV永生化角质形成细胞对肿瘤坏死因子-β和转化生长因子-β的抵抗沿着不同的调控途径进行。©1992 Wiley-Liss，Inc.
Keratinocytes immortalized by human papillomaviruses (HPV) 16 and 18 are partially resistant to the inhibition of proliferation exerted by transforming growth factor‐β (TGF‐β). To determine if this finding reflects a generalized resistance to inhibitory cytokines, we studied the effect of tumor necrosis factor‐α (TNF‐α) on subconfluent cultures of both normal and HPV‐immortalized human foreskin keratinocytes. Whereas primary and HPV‐16‐immortalized keratinocytes were sensitive to TNF‐α, HPV‐18‐immortalized keratinocytes (and those immortalized by simian virus 40) were resistant to the inhibitory effects of this cytokine. The ability of HPV‐18 to induce a more resistant phenotype correlated with its more potent in vitro transforming activity and its apparent association with more aggressive tumors. Interestingly, the state of TNF‐induced growth inhibition in normal or HPV‐16—immortalized keratinocytes was not accompanied by a reduction in the expression of c‐myc RNA or protein. This contrasts sharply with the ability of TGF‐β to inhibit c‐myc RNA expression in normal cells. Evidently, the resistance of HPV‐immortalized keratinocytes to TNF‐β and TGF‐β proceeds along different regulatory pathways. © 1992 Wiley‐Liss, Inc.