TFAP2C controls hormone response in breast cancer cells through multiple pathways of estrogen signaling

George W WOODFIELD; Annamarie D HORAN; Yizhen Chen; Ronald J WEIGEL

doi:10.1158/0008-5472.CAN-07-2293

Back

TFAP2C controls hormone response in breast cancer cells through multiple pathways of estrogen signaling

Journal article

Open access

Peer reviewed

TFAP2C controls hormone response in breast cancer cells through multiple pathways of estrogen signaling

George W WOODFIELD, Annamarie D HORAN, Yizhen Chen and Ronald J WEIGEL

Cancer research (Chicago, Ill.), Vol.67(18), pp.8439-8443

2007

DOI: 10.1158/0008-5472.CAN-07-2293

PMID: 17875680

Files and links (1)

url

https://doi.org/10.1158/0008-5472.CAN-07-2293View

Published (Version of record) Open Access

Abstract

Breast cancers expressing estrogen receptor-α (ERα) are associated with a favorable biology and are more likely to respond to hormonal therapy. In addition to ERα, other pathways of estrogen response have been identified including ERβ and GPR30, a membrane receptor for estrogen, and the key mechanisms regulating expression of ERs and hormone response remain controversial. Herein, we show that TFAP2C is the key regulator of hormone responsiveness in breast carcinoma cells through the control of multiple pathways of estrogen signaling. TFAP2C regulates the expression of ERα directly by binding to the ERα promoter and indirectly via regulation of FoxM1. In so doing, TFAP2C controls the expression of ERα target genes, including pS2, MYB, and RERG. Furthermore, TFAP2C controlled the expression of GPR30. In distinct contrast, TFAP2A, a related factor expressed in breast cancer, was not involved in estrogen-mediated pathways but regulated expression of genes controlling cell cycle arrest and apoptosis including p21CIP1 and IGFBP-3. Knockdown of TFAP2C abrogated the mitogenic response to estrogen exposure and decreased hormone-responsive tumor growth of breast cancer xenografts. We conclude that TFAP2C is a central control gene of hormone response and is a novel therapeutic target in the design of new drug treatments for breast cancer.

Antineoplastic Agents

Tumors

Gynecology. Andrology. Obstetrics

Mammary gland diseases

Pharmacology. Drug treatments

Biological and medical sciences

Medical sciences

Details

Title: Subtitle: TFAP2C controls hormone response in breast cancer cells through multiple pathways of estrogen signaling
Creators: George W WOODFIELD - Department of Surgery and Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States
Annamarie D HORAN - Department of Surgery, University of Pennsylvania, Philadelphia, Pennsylvania, United States
Yizhen Chen - Department of Surgery and Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States
Ronald J WEIGEL - Department of Surgery and Department of Biochemistry, University of Iowa Carver College of Medicine, Iowa City, Iowa, United States
Resource Type: Journal article
Publication Details: Cancer research (Chicago, Ill.), Vol.67(18), pp.8439-8443
DOI: 10.1158/0008-5472.CAN-07-2293
PMID: 17875680
NLM abbreviation: Cancer Res
ISSN: 0008-5472
eISSN: 1538-7445
Publisher: American Association for Cancer Research; Philadelphia, PA
Language: English
Date published: 2007
Academic Unit: Molecular Physiology and Biophysics; Anatomy and Cell Biology; Surgery; Biochemistry and Molecular Biology
Record Identifier: 9984024533002771

Metrics

24 Record Views

66 Times Cited - Web of Science