Synergistic effects of retinoic acid and tamoxifen on human breast cancer cells: Proteomic characterization

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-trans forming growth factor beta (TGF beta) 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 TGF beta treatment, or co-treatment with TGF beta inhibitor SB 431542, proteomic results showed that a number of proteins were involved in TGF beta signaling pathway. These results provide valuable insights into the mechanisms of RA and tamoxifen-induced TGF beta signaling pathway in breast cancer cells. (c) 2006 Elsevier Inc. All rights reserved.