Fulvestrant treatment alters MDM2 protein turnover and sensitivity of human breast carcinoma cells to chemotherapeutic drugs

Sonia C. Dolfi, Adriana V. Jäger, Daniel J. Medina, Bruce G. Haffty, Jin Ming Yang, Kim M. Hirshfield

Research output: Contribution to journalArticlepeer-review

13 Scopus citations

Abstract

The human homologue of mouse double minute 2 (MDM2) is overexpressed in tumors and contributes to tumorigenesis through inhibition of p53 activity. We investigated the effect of the anti-estrogen fulvestrant on MDM2 expression and sensitivity of estrogen receptor positive human breast cancer cell lines to chemotherapeutics. Fulvestrant down-regulated MDM2 through increased protein turnover. Fulvestrant blocked estrogen-dependent up-regulation of MDM2 and decreased basal expression of MDM2 in the absence of estradiol. As combinations of fulvestrant with doxorubicin, etoposide or paclitaxel were synergistic, altering cell cycle distribution and increasing cell death, this provides rationale for testing combinatorial chemotherapy with fulvestrant as a novel therapeutic strategy for patients with advanced breast cancer.

Original languageEnglish (US)
Pages (from-to)52-60
Number of pages9
JournalCancer Letters
Volume350
Issue number1-2
DOIs
StatePublished - Aug 1 2014

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

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