Transient stabilization of p53 in non-small cell lung carcinoma cultures arrested for growth by retinoic acid.
Transient stabilization of p53 in non-small cell lung carcinoma cultures arrested for growth by retinoic acid.
复制标题
非小细胞肺癌培养物中 p53 的瞬时稳定通过视黄酸抑制生长。
DOI：
10.1006/excr.1994.1234
复制
发表时间：
1994
影响因子：
3.7
通讯作者：
Mukhopadhyay,T
中科院分区：
文献类型：
--
作者：
Maxwell,SA;Mukhopadhyay,T
接触视黄酸 16 小时后，五种非小细胞肺癌 (NSCLC) 培养物的增殖受到抑制。我们研究了 p53 蛋白的表达是否与在视黄酸存在下观察到的 NSCLC 系的生长模式相关。在用 5 μM 视黄酸处理 16 至 48 小时后，H460a 和 H226b 系中野生型 p53 蛋白的水平增加了五倍，但在用视黄酸处理 72 小时后，这些细胞系中的野生型 p53 蛋白水平降低至不可检测的水平。在视黄酸处理的 H460a 细胞中蛋白质表达增加期间，p53 转录物水平保持不变，表明翻译后机制参与了蛋白质表达的增加。脉冲追踪分析表明，野生型 p53 在用视黄酸处理的 H460a 细胞中显着更稳定，表现出大于 6 小时的半衰期，而未经处理的对照细胞中的蛋白质半衰期为 3 小时。视黄酸介导的效应对于野生型p53是特异性的，因为即使在暴露于视黄酸72小时后，H596b和H322j细胞系中突变体p53的表达仍保持相对不变。我们得出结论，视黄酸通过翻译后机制诱导 NSCLC 细胞中野生型 p53 的稳定。此外，p53表达的增加并不是视黄酸诱导的NSCLC细胞生长短暂抑制的原因，因为视黄酸也抑制H358 p53缺失细胞的生长。
Proliferation of five non-small cell lung carcinoma (NSCLC) cultures was inhibited after 16 h exposure to retinoic acid. We investigated whether expression of the p53 protein correlated with the growth pattern of NSCLC lines observed in the presence of retinoic acid. Levels of wild-type p53 protein underwent fivefold increases in lines H460a and H226b after 16 to 48 h treatment with 5 μMretinoic acid but then decreased to undetectable amounts in these cell lines after 72 h retinoic acid treatment. Levels of p53 transcripts remained unchanged during the time of increases in protein expression in retinoic acid-treated H460a cells, suggesting that a post-translational mechanism was involved in the increased expression of the protein. Pulse—chase analysis demonstrated that wild-type p53 was significantly more stabile in H460a cells treated with retinoic acid, exhibiting a half-life greater than 6 h, in contrast to 3 h for the protein in untreated control cells. The retinoic acid-mediated effect was specific for wild-type p53, since expression of mutant p53 in the H596b and H322j cell lines remained relatively unchanged even after 72 h exposure to retinoic acid. We conclude that retinoic acid induces stabilization of wild-type p53 in NSCLC cells by a post-translational mechanism. Furthermore, increases in expression of p53 were not responsible for the retinoic acid-induced transient inhibition of growth of NSCLC cells, since the growth of H358 p53-null cells also was inhibited by retinoic acid.