Novel senescence associated gene, YPEL3, is repressed by estrogen in ER+ mammary tumor cells and required for tamoxifen-induced cellular senescence

Rebecca Tuttle, Kelly R. Miller, J. Nicholas Maiorano, Paula M. Termuhlen, Yongping Gao, Steven J. Berberich

Research output: Contribution to journalArticle

8 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)2291-2299
Number of pages9
JournalInternational Journal of Cancer
Volume130
Issue number10
DOIs
StatePublished - May 15 2012

Fingerprint

Cell Aging
Tamoxifen
Estrogens
Breast Neoplasms
Estrogen Receptors
Genes
MCF-7 Cells
Estrogen Receptor alpha
Therapeutics
Growth
Carcinogenesis
Breast
Down-Regulation
Cell Line
Neoplasms
Proteins

Keywords

  • YPEL3
  • cellular senescence
  • estrogen receptor
  • p53
  • tamoxifen

Cite this

Novel senescence associated gene, YPEL3, is repressed by estrogen in ER+ mammary tumor cells and required for tamoxifen-induced cellular senescence. / Tuttle, Rebecca; Miller, Kelly R.; Maiorano, J. Nicholas; Termuhlen, Paula M.; Gao, Yongping; Berberich, Steven J.

In: International Journal of Cancer, Vol. 130, No. 10, 15.05.2012, p. 2291-2299.

Research output: Contribution to journalArticle

Tuttle, Rebecca ; Miller, Kelly R. ; Maiorano, J. Nicholas ; Termuhlen, Paula M. ; Gao, Yongping ; Berberich, Steven J. / Novel senescence associated gene, YPEL3, is repressed by estrogen in ER+ mammary tumor cells and required for tamoxifen-induced cellular senescence. In: International Journal of Cancer. 2012 ; Vol. 130, No. 10. pp. 2291-2299.
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