에스트로젠이 사람 유방암 세포 증식과 쥐의 간 및 자궁의 이물 대사 효소에 미치는 영향

Abstract

Estrogen, estrogen길항제와 3-methylcholanthrene이 사람 유방암 세포인 MCF-7세포의 증식에 미치는 영향을 조사하기위해서 estradiol, tamoxifen, 3-methylchlanthrene을 투여했을 때, estradiol은 MCF-7세포의 증식을 3.8배증가시켰고, 이러한 estrogen의 효과는 tamoxifen의 병용 투여에 의해서 억제되었다. Tamoxifen과 3-methylcholanthrene은 그 자체만 투여하였을 때에는 MCF-7세포의 성장에 별다른 영향을 미치지 못하였다. 또한 이러한 물질이 cytochorome P450 동종 효소인 ethoxyresorufin deethylase에 미치는 영향을 조사하기위해서 MCF-7세포와 미성숙 자성 백서의 간과 자궁에서 fluorometer방법을 이용하여 효소 활성을 측정하였다. 3-Methylcholanthrene을 처치한 쥐의 간에서는 대조군과 비교시 ethoxyresorufin deethylase 활성이 1.9배 증가하였으나, 쥐의 자궁과 MCF-7세포는 대조군과 비교하였을 때 변화가 없었다. UDP-glucuronosyltransferase 유전자 조절에 미치는 estradiol, tamoxifen, 그리고 3-methylcholanthrene의 영향을 살펴보기 위해 MCF-7세포와 쥐의 자궁에 UDPGT_(h)-2 cDNA를 probe으로 이용하여 dot hybridization을 실시하였다. Estorgen투여는 UDPGT_(h)-2 mRNA양을 증가시키며 이러한 효과는 tamoxifen의 병용 투여에 의해서 억제되지 않았다.;To investigate the effects of estrogen, antiestrogen and 3-methylcholanthrene on the proliferation of MCF-7, human breast cancer MCF-7 cells were treated with estradiol, tamoxifen, and 3-methylcholanthrene. 17β -estradiol increased the proliferaion of MCF-7 cells by 3.8 fold, but this stimulated estrogenic effect was blocked by concomitant treatment of antiestrogen, tamoxifen. Tamoxifen and 3-methylcholanthrene had little effect on MCF-7 cell growth when it was administrated alone. Furthermore, study bas been conducted to examine the effects of estradiol, tamoxifen, 3-methylcholanthrene on ethoxyresorufin deethylase activities in MCF-7 cells, immature female rat liver and uterus via fluorometric assay. Ethoxyresorufin deethylase activity of 3-methylcholanthrene treated rat liver was increased by 1.9 fold compared with that of control. However, ethoxyresorufin deethylase activity of 3-methylcholanthrene treated rat uterus and MCF-7 cells were not changed compared with that of control. In order to understand the effects of estradiol, tamoxifen, and 3-methylcholanthrene on the regulation of UDP-glucuronosyltransferase gene expression, dot hybridization was carried out using UDPGT_(h)-2 cDNA as a probe in rat uterus and human breast cancer MCF-7 cells. The data showed that estrogen increase the level of mRNA of UDPGT_(h)-2 that is responsable for excretion of estrogen and this estrogen effect was not blocked by tamoxifen which was treated concomitantly.