人类胰岛素样生长因子—I调控子宫内膜癌细胞系孕激素受体亚型表达的研究

目的 探讨不同剂量人类胰岛素样生长因子－I（IGF－I）对子宫内膜癌细胞系中孕激素受体亚型表达的动态变化的调控。方法 体外培养子宫内膜癌细胞系HEC－IB,以乳腺癌细胞系MCF－7为对照,采用蛋白印迹（Western blot)法观察不同剂量IGF－I对两种孕激素受体亚型表达的动态变化的调控。结果 （1）HEC－IB细胞中,IGF－I 10ng/ml作用24h,人孕激素受体B亚型（hPRB)表达有明显上调作用,随着剂量的增加、作用时间的延长,pPRB表达逐渐下调,IGF－I 20ng/ml作用72h及40ng/ml作用48h时,下调最明显。人孕激素受体A亚型（hPRA)表达的变化趋势与hPRB大致相同,IGF－I为20ng/ml作用48h时下调至最低。（2）MCF－7细胞中,IGF－I 10、40ng/ml对hPRA、hPRB表达均有上调的作用,在第24、48、72h时较为明显。IGF－I 20ng/ml作用24h对hPRB表达有上调的作用,但在48、72h出现明显的下调;而对hPRA表达均为下调作用。结果 （1）IGF－I对人孕激素受体亚型的调控具有细胞特异性、以及时间和剂量的依赖性。（2）HEC－IB细胞中,IGF－I 10ng/ml作用24h对hPRA、hPRB表达有上调作用,随着剂量的增加、作用时间的延长,hPRA、hPRB表达渐下调。

Time-dependent and dose-dependent regulation of human progesterone receptor isoforms A and B in uterine endometrial carcinoma by human insulin-like growth factor-I

OBJECTIVE: We study the regulation of human progesterone receptor isoforms A and B in uterine endometrial carcinoma cell line by different concentration of human insulin-like growth factor-I (IGF-I) for different time, to investigate the roles of IGF-I and progesterone receptor isoforms in uterine endometrial carcinoma. METHODS: The uterine endometrial adenocarcinoma cell line HEC-IB was cultured in vitro and the breast cancer cell line MCF-7 was used as control. Western blot was applied to examine the changes of the two isoforms by different concentration IGF-I for different time. RESULTS: (1) In HEC-IB cell line, 10 ng/ml IGF-I made hPRB up-regulated in the first 24 h. But according to lager concentration and longer time, human progesterone receptor (hPR) B became down-regulated, which were significant at 20 ng/ml IGF-I for 72 h and 40 ng/ml IGF-I for 48 - 72 h.The change of hPRA was like hPRB. (2) In MCF-7 cell line, 10 ng/ml and 40 ng/ml IGF-I made hPRA and hPRB significantly up-regulated in 24, 48, 72 h. Twenty ng/ml IGF-I made hPRB up-regulated also in the first 24 h. But in 48 h and 72 h, down-regulation of hPRB was detected. Twenty ng/ml IGF-I made hPRA down-regulated in 24, 48, 72 h. CONCLUSIONS: (1) The regulation of IGF-I to hPR isoforms has cell-type specific and dose-dependent and time-dependent. (2) In HEC-IB cell line, 10 ng/ml IGF-I made hPRB significantly up-regulated in 24 h. But following exposure to IGF-I at larger concentration and longer time, hPRB became down-regulated. The change of hPRA is like hPRB.