title: Novel senescence associated gene, YPEL3, is repressed by estrogen in ER+ mammary tumor cells and required for tamoxifen-induced cellular senescence.
abstract: Estrogen signaling plays an important role in breast carcinogenesis. An increased understanding of estrogen gene targets and their effects will allow for more directed and effective therapies for individuals with breast cancer, particularly those with estrogen receptor positive tumors resistant to tamoxifen therapy. Here, we identify YPEL3 as a growth suppressive protein downregulated by estrogen in estrogen receptor positive breast cancer cell lines. Estrogen repression of YPEL3 expression was found to be independent of p53 but dependent on estrogen receptor alpha expression. Importantly, YPEL3 expression, which is induced by the removal of estrogen or treatment with tamoxifen triggers cellular senescence in MCF-7 cells while loss of YPEL3 increases the growth rate of MCF-7 cells. Taken together these findings suggest that YPEL3 may represent a potential target for directed hormonal therapy for estrogen receptor positive breast cancer patients.
authors.affiliation: Biochemistry and Molecular Biology Department, Wright State University, Dayton, OH, USA.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Tuttle
authors.forename: Kelly R
authors.initials: KR
authors.lastname: Miller
authors.forename: J Nicholas
authors.initials: JN
authors.lastname: Maiorano
authors.forename: Paula M
authors.initials: PM
authors.lastname: Termuhlen
authors.forename: Yongping
authors.initials: Y
authors.lastname: Gao
authors.forename: Steven J
authors.initials: SJ
authors.lastname: Berberich
mesh_terms: D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000235:genetics; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects*; D004967:Estrogens; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D009376:Neoplasms, Hormone-Dependent; D011960:Receptors, Estrogen / Q000378:metabolism*; D013629:Tamoxifen / Q000494:pharmacology*; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D018931:Antineoplastic Agents, Hormonal; D004967:Estrogens; D011960:Receptors, Estrogen; D025521:Tumor Suppressor Proteins; C549565:YPEL3 protein, human; D013629:Tamoxifen