外遺傳分析肌動素調節蛋白在TGF-beta 1誘導分化人乳癌幹細胞與鼻咽癌幹細胞的表現

Abstract

Breast cancer is one of most common cause of cancer death in the world. Approximately 5% of patients with breast cancer have clinically detectable metastases at the time of initial diagnosis and 30-40% of patients who appear clinically free of metastases accumulate hidden metastases. Presumably, tumor cells shed from the primary lesions are released into the peripheral circulation as circulating tumor cells (CTCs), and then CTCs migrate to the bone marrow microenvironment where there is a selection to maintain a non-proliferative stem cell like phenotype or to be induced to become cancer-initiating stem cells (CSCs) for metastases. Gelsolin (GSN) is an actin-binding protein encoded by the gene, which is located at human chromosome 9q33. GSN is known to regulate cell morphology, motility, differentiation, and apoptosis. Down-regulation of GSN was found in many types of human malignant cancers. However, the role of GSN in cancer stem cell has not been well evaluated. In this study, we demonstrated that GSN expression was decreased in CD44+/CD24- subpopulation of MDA-MB-231 breast cancer cells and HONE-1 nasopharyngeal carcinoma cells without TGF-beta 1 treatment, while GSN expression was increased with TGF-beta 1 treatment. The increased GSN expression was accompanied by increased cell migration and invasion for TGF-beta 1 treated cells. Epigenetic analysis showed that TGF-beta 1 caused to modify GSN expression in both MDA-MB-231 cells and HONE-1 cells through epigenetic alteration in chromatin structure. In summary, the results found in this study suggest that TGF-beta 1 induction attenuated the methylation but facilitated the unmethylation on GSN DNA promoter region such as that increased GSN expression in cancer cells.