유방암 세포에서 Tamoxifen과 Retinoic Acid가 Transforming Growth Factor-β에 미치는 영향

Abstract

TGF-b is multifunctional regulatory homodimeric polypeptides and reaulate cell differentiation, cell growth, cell function and is the most potent growth-inhibitory polypeptides known for a wide variety of cell types including most normal and transformed epithelial, endothelial, fibroblast, lymphoid and hematopoietic cells. The production of TGF-b by the estrogen receptor-positive cell line MCF-7 has been reported to be most affected by antiestrogens, and Tamoxifen caused a 5-fold increase in production of TGF-b by MCF-7 cells and its regulation of TGF-b production was thought to be posttranscriptional. Recent work has shown that the proliferation of both mouse and human keratinacytes was potentially and reversibly inhibited by TGF-b, and that retinoic acid induced TGF-b1 in cultured keratinocytes and mouse epidermis. These results suggest that the regulation of TGF-b2, expression by tamoxifen and retinoic acid may have a important role in control of breast cancer cell growth. To obtain better understanding of how tamoxifen and retinoic acid could regulate growth of breast cancer cells, we carried out this experimental study. Using phenol red-free medium, we cultured MCF-7 cells and then treated with various dosage of tamoxifen, retinoic acid and tamoxifen with retinoic acid, and then observed MCF-7 cell growth and the production of TGF-b. The growth of MCF-7 cell was markedly inhibited by tamoxifen, and synergistic inhibitory effect was discovered when retinoic acid was supplemented with tamoxifen. Both tamoxifen and retinoic acid increased the secretion of TGF-b1, & TGF-b2, especially TGF-b2. The mRNA induction of TGF-b2 was increased by treatment of retinoic acid and it was more increased by treatment of retinoic acid with tamoxifen. As these results, we concluded that Tamoxifen and retinoic acid increased the production of the TGF-b2 retinoic acid may be used as second postoperative adjuvant therapeutic agent of breast cancer.