Effects of 12-O-tetradecanoylphorbol-13-acetate on human papillomavirus type 16-positive keratinocytes at different stages of transformation.
Effects of 12-O-tetradecanoylphorbol-13-acetate on human papillomavirus type 16-positive keratinocytes at different stages of transformation.
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12-O-十四烷酰佛波醇-13-乙酸酯对不同转化阶段的人乳头瘤病毒 16 型阳性角质形成细胞的影响。
DOI：
10.1002/mc.2940130304
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发表时间：
1995
影响因子：
4.6
通讯作者：
Braun,L
中科院分区：
文献类型：
--
作者：
Sears,WL;Goto-Mandeville,R;Mirapuri,M;Braun,L
在无血清条件下生长的正常人角质形成细胞可以通过暴露于血清或佛波酯12-O-十四酰佛波醇-13-醋酸酯(TPA)而被触发分化。我们发现，TPA处理培养中的人乳头瘤病毒(HPV)16型永生化细胞，诱导形成角化的囊膜，表明鳞状细胞分化。在分化的同时，TPA抑制HPV16E6和E7mRNA的表达。永生化细胞对含血清培养基中生长的适应导致了对TPA诱导分化具有抗性的HPV转化细胞亚群的选择。在该细胞系中，HPV转录本在5h出现一过性抑制，而在分化耐药、肿瘤来源的细胞系中，TPA对HPV癌基因的表达几乎没有影响，只有分化能力强的细胞在TPA作用下c-myc转录本被抑制，c-fos和c-jun在所有细胞系中都被瞬时诱导。当HPV16永生化细胞被诱导分化时，转化生长因子-α的mRNAs也增加了大约8倍。这些结果表明，在HPV16永生化角质形成细胞中，对鳞状分化诱导剂的抵抗力的获得伴随着细胞生长和基因表达的调节改变。©1995 Wiley-Liss公司
Normal human keratinocytes grown under serum‐free conditions can be triggered to differentiate by exposure to serum or to the phorbol ester 12‐O‐tetradecanoylphorbol‐13‐acetate (TPA). We found that TPA treatment of human papillomavirus (HPV) type 16‐immortalized cells in culture induced formation of cornified envelopes indicative of squamous differentiation. Concurrent with differentiation, TPA inhibited the expression of HPV 16 E6 and E7 mRNA transcripts. Adaptation of the immortalized cells to growth in serum‐containing medium led to the selection of a subpopulation of HPV‐transformed cells that was resistant to TPA‐induced differentiation. In this cell line, a transient suppression of HPV transcripts was observed at 5 h, whereas in differentiation‐resistant, carcinoma‐derived lines, TPA had little effect on HPV oncogene expression, c‐myctranscripts were suppressed for the duration of exposure to TPA in only the differentiation‐competent cells; c‐fosand c‐junwere transiently induced in all cell lines. Transforming growth factor‐a mRNAs were also increased approximately eightfold as HPV 16‐immortalized cells were induced to differentiate. These results demonstrate that, in HPV 16‐immortalized keratinocytes, acquisition of resistance to inducers of squamous differentiation is accompanied by altered regulation of cell growth and gene expression. © 1995 Wiley‐Liss, Inc.