Hormonal regulation of apoptosis in breast cells and tissues
Hormonal regulation of apoptosis in breast cells and tissues
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DOI：
10.1016/s0039-128x(00)00172-0
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发表时间：
2000-10-01
期刊：
影响因子：
2.7
通讯作者：
Rostène, W
中科院分区：
文献类型：
--
作者：
Gompel, A;Somai, S;Rostène, W
很少有研究涉及激素治疗后细胞凋亡过程的影响。没有关于孕酮对乳腺细胞影响的数据。为了进一步了解性腺激素和抗雌激素在乳腺细胞中的作用，我们在不同的乳腺材料中进行了细胞凋亡的研究。我们已经开发了一个正常乳腺细胞的模型，在培养中仍然依赖激素。在这些细胞和一些激素依赖性乳腺癌细胞系（T-47-D, ZR75-1, MCF-7）中，我们观察到雌二醇（E-2）的抗凋亡作用和一些抗雌激素的有效促凋亡作用。孕激素在正常和激素依赖性乳腺癌细胞中也有促凋亡作用。为了了解这些激素对细胞凋亡的作用机制，我们对bcl-2家族蛋白进行了研究，结果表明，E-2增加了抗凋亡蛋白bcl-2和bclx(L)的表达，而孕激素显著降低了bcl-2的表达和bclx(L)的表达。我们研究了E-2增加bcl-2表达的机制。我们使用定量RT-PCR的结果显示，E-2通过转录机制在48小时后增加了bcl-2 mRNA的表达。激素治疗均未改变促凋亡蛋白bax和bak水平。我们还根据月经周期研究了正常乳腺组织活检中bcl-2及其家族成员的体内表达情况。Bcl-2表现出强烈的周期性变异，似乎是家族中最依赖激素的成员。(C) 2000 Elsevier Science Inc.；版权所有。
Few studies have referred to the implication of apoptotic processes following hormonal treatment. No data are available on the effects of progesterone in breast cells. In order to gain insights on the effects of the gonadal steroids and antiestrogens in breast cells, we have carried out studies on apoptosis in different breast materials. We have developed a model of normal breast cells in cultures that remain hormone-dependent. On these cells and in some hormone-dependent breast cancer cell lines (T-47-D, ZR75-1, MCF-7) we have observed an antiapoptotic effect of estradiol (E-2) and a potent proapoptotic effect of some antiestrogens. Progestins were also proapoptotic in normal as well as in hormone-dependent breast cancer cells. In order to understand the mechanisms of these hormones on apoptosis, we studied the bcl-2 family proteins, We demonstrated that E-2 increased the antiapoptotic proteins, bcl-2 and bclx(L), whereas, the progestins drastically decreased bcl-2 expression and weakly bclx(L) levels. We investigated the mechanisms by which E-2 increased bcl-2 expression Our results using quantitative RT-PCR showed that E-2 increased bcl-2 mRNA levels at 48 h of treatment via a transcriptional mechanism. None of the hormone treatments altered the proapoptotic protein levels, bax and bak. We also studied the in vivo expression of bcl-2 and other members of its family in biopsies of normal breast tissues according to the menstrual cycle. Bcl-2 displayed a strong cyclical variation and seemed to be the most hormone-dependent member of the family. (C) 2000 Elsevier Science Inc. All rights reserved.