1. Methylation of RASSF10 promotes cell proliferation and serves as a docetaxel resistant marker in human breast cancer.
- Author
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Dong T, Zhang M, Dong Y, Herman JG, van Engeland M, Zhong G, and Guo M
- Subjects
- Biomarkers, Tumor genetics, Breast Neoplasms, DNA, Neoplasm genetics, DNA, Neoplasm metabolism, Docetaxel, Female, Gene Expression Regulation, Neoplastic drug effects, Humans, MCF-7 Cells, Signal Transduction drug effects, Tumor Suppressor Protein p53 genetics, Tumor Suppressor Protein p53 metabolism, Tumor Suppressor Proteins genetics, Biomarkers, Tumor biosynthesis, Cell Proliferation drug effects, DNA Methylation, Drug Resistance, Neoplasm drug effects, Taxoids pharmacology, Tumor Suppressor Proteins biosynthesis
- Abstract
Breast cancer is a leading cause of death among females worldwide. However, the mechanisms of breast cancer remain largely unclear. RASSF10 is frequently methylated in certain types of human cancers. To understand the mechanism of RASSF10 in breast cancer, samples of breast cancer cell lines, primary cancer, breast tissue adjacent to cancer, and normal breast tissue were investigated in this study. Methylation specific PCR (MSP), flow cytometry, western blot, and siRNA knockdown assay were used. Complete methylation was found in MCF7, MDA-MB-435, and MDA-MB-468 cells, partial methylation was found in ZR75-1 cells, and unmethylation was revealed in SKBR3 cells. Loss of RASSF10 expression was found in MCF7, MDA-MB-435, and MDA-MB-468 cells, and high expression of RASSF10 was found in ZR75-1 and SKBR3 cells. The expression of RASSF10 was induced by 5-aza-2'-deoxycytidine (5-Aza) in MCF7, MDA-MB-435, and MDA-MB-468 cells. RASSF10 methylation was found in 77.8% (49/63) of primary breast cancer and 17.8% (8/45) of adjacent tissue samples. No methylation was found in normal breast tissue samples. Restoration of RASSF10 expression inhibited cell proliferation and induced G2/M phase arrest in MCF7 and MDA-MB-468 cells. RASSF10 sensitized these cells to docetaxel. RASSF10 induced apoptosis and activated P53 signaling in breast cancer cells. In conclusion, RASSF10 is frequently methylated in human breast cancer and infrequently in adjacent tissue samples. RASSF10 methylation may serve as an early detective marker. The expression of RASSF10 is regulated by promoter region methylation. Since restoration of RASSF10 expression sensitized breast cancer cells to docetaxel, RASSF10 methylation is a potential docetaxel resistant marker. RASSF10 suppresses breast cancer growth by activating P53 signaling.
- Published
- 2015