Wang Ying, He Qing-Yu, Chen Hongming, Chiu Jen-Fu
Department of Chemistry, The University of Hong Kong, Pokfulam, Hong Kong SAR, China.
Exp Cell Res. 2007 Jan 15;313(2):357-68. doi: 10.1016/j.yexcr.2006.10.016. Epub 2006 Oct 25.
The anti-estrogen tamoxifen and vitamin A-related compound, all-trans retinoic acid (RA), in combination act synergistically to inhibit the growth of MCF-7 human breast cancer cells. In the present study, we applied two-dimensional gel electrophoresis based proteomic approach to globally analyze this synergistic effect of RA and tamoxifen. Proteomic study revealed that multiple clusters of proteins were involved in RA and tamoxifen-induced apoptosis in MCF-7 breast cancer cells, including post-transcriptional and splicing factors, proteins related to cellular proliferation or differentiation, and proteins related to energy production and internal degradation systems. The negative growth factor-transforming growth factor beta (TGFbeta) was secreted by RA and/or tamoxifen treatment and was studies as a potential mediator of the synergistic effects of RA and tamoxifen in apoptosis. By comparing protein alterations in treatments of RA and tamoxifen alone or in combination to those of TGFbeta treatment, or co-treatment with TGFbeta inhibitor SB 431542, proteomic results showed that a number of proteins were involved in TGFbeta signaling pathway. These results provide valuable insights into the mechanisms of RA and tamoxifen-induced TGFbeta signaling pathway in breast cancer cells.
抗雌激素他莫昔芬和维生素A相关化合物全反式维甲酸（RA）联合使用时具有协同作用，可抑制MCF-7人乳腺癌细胞的生长。在本研究中，我们应用基于二维凝胶电泳的蛋白质组学方法全面分析RA和他莫昔芬的这种协同作用。蛋白质组学研究表明，多个蛋白质簇参与了RA和他莫昔芬诱导的MCF-7乳腺癌细胞凋亡，包括转录后和剪接因子、与细胞增殖或分化相关的蛋白质，以及与能量产生和内部降解系统相关的蛋白质。负生长因子转化生长因子β（TGFβ）由RA和/或他莫昔芬处理分泌，并被作为RA和他莫昔芬在凋亡中协同作用的潜在介质进行研究。通过比较单独或联合使用RA和他莫昔芬处理与TGFβ处理或与TGFβ抑制剂SB 431542共同处理时的蛋白质变化，蛋白质组学结果表明许多蛋白质参与了TGFβ信号通路。这些结果为RA和他莫昔芬诱导乳腺癌细胞中TGFβ信号通路的机制提供了有价值的见解。
