Gelsolin expression modulates TGF‐beta induced cell differentiation and epithelial to mesenchymal transition in breast cancer cells (694.3)

Abstract

Gelsolin (GSN) is one of actin filament‐severing proteins that play a key role in the actin cytoskeleton rearrangement and the modification of tumor cell proliferation and metastasis. TGF‐beta has been shown to initiate the Epithelial to Mesenchymal Transition (EMT) in breast cancer cells. However, the relationship between the expression level of GSN and the TGF‐beta signaling for cell differentiation and EMT progression is not clear. In this study, MDA‐MB‐231 human breast cancer cells were treated with 2 ng/ml TGF‐beta1 for 3 days, and the population of CD44+/CD24‐ cells were sorted out by flow cytometry. These cells were found to increase the gene markers for stem cell pluripotency (i.e. Oct4, Sox2 and Nanog), associated with increased expression for mesenchymal cell markers such as N‐cadherin, and vimentin, and with a concomitant decrease for epithelial marker such as E‐cadherin. In addition, TGF‐beta1 induced an increased gene expression for GSN but decreased expressions for the two DNA methyltransferases, DNMT1and DNMT3B. Methylation specific PCR analysis also showed that TGF‐beta1 caused a 50% decrease in methylation with concomitant 3‐fold increases in unmethylation on the CpG island at the GSN promotor in the CD44+ cells. These results indicated that TGF‐beta1 induced epigenetic modification of GSN might be responsible for the cancer stem cell signaling in breast cancer cells.Grant Funding Source: Supported by NSC 102‐2320‐B‐005‐002