title: REGγ regulates ERα degradation via ubiquitin-proteasome pathway in breast cancer.
abstract: REGγ is a proteasome coactivator which regulates proteolytic activity in eukaryotic cells. Abundant lines of evidence have showed that REGγ is over expressed in a number of human carcinomas. However, its precise role in the pathogenesis of cancer is still unclear. In this study, by examining 200 human breast cancer specimens, we demonstrated that REGγ was highly expressed in breast cancers, and the expression of REGγ was positively correlated with breast cancer patient estrogen receptor alpha (ERα) status. Moreover, the expression of REGγ was found positively associated with poor clinical features and low survival rates in ERα positive breast cancer patients. Further cell culture studies using MCF7 and BT474 breast cancer cell lines showed that cell proliferation, motility, and invasion capacities were decreased significantly by REGγ knockdown. Lastly, we demonstrated that REGγ indirectly regulates the degradation of ERα protein via ubiquitin-proteasome pathway. In conclusion, our findings provide the evidence that REGγ expression was positively correlated with ERα status and poor clinical prognosis in ERα positive breast cancer patients. As well, we disclose a new connection between the two molecules that are both highly expressed in most breast cancer cases.
authors.affiliation: Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Chai
authors.affiliation: Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Liang
authors.affiliation: Laboratory of General Surgery, First Affiliated Hospital, Sun Yet-sen University, Guangzhou 510080, China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Bi
authors.affiliation: Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Li
authors.initials: L
authors.lastname: Chen
authors.affiliation: Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Fan
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Institute of Pathology and Southwest Cancer Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors.forename: Youhong
authors.initials: Y
authors.lastname: Cui
authors.affiliation: Breast Disease Center, Southwest Hospital, Third Military Medical University, Chongqing 400038, China. Electronic address: jcbd@medmail.com.cn.
authors.forename: Jun
authors.initials: J
authors.lastname: Jiang
mesh_terms: D000328:Adult; D000368:Aged; D001324:Autoantigens / Q000378:metabolism*; D001943:Breast Neoplasms / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D047628:Estrogen Receptor alpha / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D061986:MCF-7 Cells; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000378:metabolism; D025801:Ubiquitin / Q000378:metabolism*
chemical_list: D001324:Autoantigens; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha; C099558:Ki antigen; D034741:RNA, Small Interfering; D025801:Ubiquitin; D046988:Proteasome Endopeptidase Complex
keywords: Breast cancer; Degradation; ERα; Proteasome; REGγ; Ubiquitin