title: Methylation of RASSF10 promotes cell proliferation and serves as a docetaxel resistant marker in human breast cancer.
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.
authors.affiliation: Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Tenghui
authors.initials: T
authors.lastname: Dong
authors.affiliation: Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing 100853, China.|Medical College of NanKai University, Tianjin 300071, China.
authors.forename: Meiying
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Dong
authors.affiliation: The Hillman Cancer Center, University of Pittsburgh Cancer Institute, Pittsburgh, PA 15213, USA.
authors.forename: James G
authors.initials: JG
authors.lastname: Herman
authors.affiliation: Department of Pathology, GROW-School for Oncology and Developmental Biology, Maastricht University Medical Center, Maastricht, the Netherlands.
authors.forename: Manon
authors.initials: M
authors.lastname: van Engeland
authors.affiliation: Department of Internal Medicine, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Guanglin
authors.initials: G
authors.lastname: Zhong
authors.affiliation: Department of Gastroenterology and Hepatology, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: Mingzhou
authors.initials: M
authors.lastname: Guo
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D001943:Breast Neoplasms; D049109:Cell Proliferation / Q000187:drug effects*; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D061986:MCF-7 Cells; D015398:Signal Transduction / Q000187:drug effects; D043823:Taxoids / Q000494:pharmacology*; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm; C548440:RASSF10 protein, human; C495901:TP53 protein, human; D043823:Taxoids; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D000077143:Docetaxel