Faculty Collaboration Database

Novel senescence associated gene, YPEL3, is repressed by estrogen in ER+ mammary tumor cells and required for tamoxifen-induced cellular senescence. Int J Cancer 2012 May 15;130(10):2291-9

Date

06/15/2011

Pubmed ID

21671470

Pubmed Central ID

PMC3247654

DOI

10.1002/ijc.26239

Scopus ID

2-s2.0-84859101069 (requires institutional sign-in at Scopus site)   28 Citations

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.

Author List

Tuttle R, Miller KR, Maiorano JN, Termuhlen PM, Gao Y, Berberich SJ

MESH terms used to index this publication - Major topics in bold

Antineoplastic Agents, Hormonal
Breast Neoplasms
Cell Line, Tumor
Cellular Senescence
Estrogens
Female
Gene Expression Regulation, Neoplastic
Humans
Neoplasms, Hormone-Dependent
Receptors, Estrogen
Tamoxifen
Tumor Suppressor Proteins