Programmed cell death during regression of the MCF-7 human breast cancer following estrogen ablation.
Programmed cell death during regression of the MCF-7 human breast cancer following estrogen ablation.
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发表时间：
1991
期刊：
影响因子：
11.2
通讯作者：
N. Kyprianou;H. English;N. Davidson;J. Isaacs
中科院分区：
文献类型：
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作者：
N. Kyprianou;H. English;N. Davidson;J. Isaacs
为了研究雌激素消融后人乳腺癌消退的机制，将雌激素应答的MCF-7人乳腺癌细胞接种到卵巢切除的雌性裸鼠体内，通过E2植入物补充外源性17 β-雌二醇（E2）。当MCF-7肿瘤大小为400 mm 3时，取出植入物。移除E2植入物导致E2消融后2周肿瘤消退50%。与这种回归相关的是一种快速的（即，在E2去除后1天内）增强转化生长因子β 1和TRPM-2基因的表达，这两种基因的表达先前已被证明在被诱导经历程序性细胞死亡的多种细胞类型中增强（即，凋亡）。转化生长因子β 1和TRPM-2的表达增强不是非特异性反应，因为其他基因如c-fos、c-H-ras和pS2的表达在E2消融后降低。肿瘤DNA分裂成核小体寡聚体和凋亡小体的组织学外观是E2消融后肿瘤体积急剧减小之前的特征性早期事件。这些结果表明，雌激素消融后裸鼠中MCF-7人乳腺癌的消退是由于一系列生物化学和形态学变化，这些变化导致细胞增殖停止和这些MCF-7癌细胞的程序性死亡或凋亡的激活。澄清参与激活这种程序性细胞死亡的生化途径，应确定新的治疗目标，即使是雌激素非依赖性人乳腺癌细胞。
To study the mechanism of regression of human mammary cancer following estrogen ablation, estrogen-responsive MCF-7 human mammary adenocarcinoma cells were inoculated into ovariectomized female nude mice supplemented with exogenous 17 beta-estradiol (E2) via an E2 implant. Implants were then removed when MCF-7 tumors were 400 mm3 in size. Removal of the E2 implants resulted in a 50% tumor regression by 2 weeks following E2 ablation. Associated with this regression is a rapid (i.e., within 1 day following E2 ablation) enhanced expression of the transforming growth factor beta 1 and TRPM-2-genes, two genes the expression of which has been previously demonstrated to be enhanced in a variety of cell types induced to undergo programmed cell death (i.e., apoptosis). The enhanced expression of transforming growth factor beta 1 and TRPM-2 is not a nonspecific response since the expression of other genes, like c-fos, c-H-ras, and pS2, decrease following E2 ablation. Fragmentation of tumor DNA into nucleosomal oligomers and histological appearance of apoptotic bodies are characteristic early events that precede the dramatic reduction in tumor volume following E2 ablation. These results demonstrate that the regression of MCF-7 human mammary cancers in nude mice following estrogen ablation is due to a sequence of biochemical and morphological changes that result in both the cessation of cell proliferation and activation of programmed death or apoptosis of these MCF-7 cancer cells. Clarification of the biochemical pathway involved in the activation of this programmed cell death should identify new targets of therapy for even estrogen-independent human mammary cancer cells.