MDM2 enhances the function of estrogen receptor in human breast cancer cells

Shigehira Saji, Naoki Okumura, Hidetaka Eguchi, Shigeru Nakashima, Akio Suzuki, Masakazu Toi, Yoshinori Nozawa, Shigetoyo Saji, Shin ichi Hayashi

Research output: Contribution to journalArticlepeer-review

80 Citations (Scopus)

Abstract

Overexpression of the oncoprotein MDM2, a negative feedback regulator of p53, is often observed in breast cancer tissue and cell lines, particularly in those which express estrogen receptor α (ERα). In this study, we report a novel function of MDM2, i.e., as a positive regulator of ERα. This function does not involve p53. MDM2 overexpressing clones derived from the breast cancer cell line, MCF-7 cells, showed a remarkable growth advantage only in estradiol supplemented conditions, and this profile coincided with increased transcriptional activity of ERa in these cells. Though p53 has been reported to be an inhibitor of ERα function, p53 protein in MDM2 overexpressing clones was more abundant than in the parental cells. When ERα was exogenously expressed in p53-null cells, its activity was enhanced by coexpression of MDM2. Mammalian two-hybrid assays and GST pull-down assays indicated that MDM2 could interact with ERα. These results indicate that MDM2 is a direct activator of ERα function, and suggest such a role for MDM2 in ERα-positive breast cancer.

Original languageEnglish
Pages (from-to)259-265
Number of pages7
JournalBiochemical and biophysical research communications
Volume281
Issue number1
DOIs
Publication statusPublished - 2001
Externally publishedYes

Keywords

  • Breast cancer
  • Estrogen receptor
  • MCF-7
  • MDM2
  • P53

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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