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

doi:10.1016/j.canlet.2014.04.009

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 journal › Article › peer-review

21 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 language	English
Pages (from-to)	52-60
Number of pages	9
Journal	Cancer Letters
Volume	350
Issue number	1-2
DOIs	https://doi.org/10.1016/j.canlet.2014.04.009
State	Published - Aug 1 2014

Bibliographical note

Funding Information:
We thank J. Harris at Rutgers Cancer Institute of New Jersey. This research was supported by the Department of Defense [Breast Cancer Research Program under award number ( W81XH-07-1-0403 )]. Views and opinions of, and endorsements by the author(s) do not reflect those of the US Army or the Department of Defense.

Keywords

Breast cancer
Chemotherapy
Estrogen receptor
Fulvestrant
MDM2

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.canlet.2014.04.009

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

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.",

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note = "Funding Information: We thank J. Harris at Rutgers Cancer Institute of New Jersey. This research was supported by the Department of Defense [Breast Cancer Research Program under award number ( W81XH-07-1-0403 )]. Views and opinions of, and endorsements by the author(s) do not reflect those of the US Army or the Department of Defense.",

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AU - Jäger, Adriana V.

AU - Medina, Daniel J.

AU - Haffty, Bruce G.

AU - Yang, Jin Ming

AU - Hirshfield, Kim M.

N1 - Funding Information: We thank J. Harris at Rutgers Cancer Institute of New Jersey. This research was supported by the Department of Defense [Breast Cancer Research Program under award number ( W81XH-07-1-0403 )]. Views and opinions of, and endorsements by the author(s) do not reflect those of the US Army or the Department of Defense.

PY - 2014/8/1

Y1 - 2014/8/1

N2 - 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.

AB - 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.

KW - Breast cancer

KW - Chemotherapy

KW - Estrogen receptor

KW - Fulvestrant

KW - MDM2

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

Abstract

Bibliographical note

Keywords

ASJC Scopus subject areas

UN SDGs

Access to Document

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