Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2007 Jul 1;67(13):6477-83.
doi: 10.1158/0008-5472.CAN-07-0746.

Positive cross-regulatory loop ties GATA-3 to estrogen receptor alpha expression in breast cancer

Jérôme Eeckhoute  1 , Erika Krasnickas Keeton, Mathieu Lupien, Susan A Krum, Jason S Carroll, Myles Brown
Affiliations

Positive cross-regulatory loop ties GATA-3 to estrogen receptor alpha expression in breast cancer

Jérôme Eeckhoute et al. Cancer Res. .

Abstract

The transcription factor GATA-3 is required for normal mammary gland development, and its expression is highly correlated with estrogen receptor alpha (ER alpha) in human breast tumors. However, the functional role of GATA-3 in ER alpha-positive breast cancers is yet to be established. Here, we show that GATA-3 is required for estradiol stimulation of cell cycle progression in breast cancer cells. The role of GATA-3 in estradiol signaling requires the direct positive regulation of the expression of the ER alpha gene itself by GATA-3. GATA-3 binds to two cis-regulatory elements located within the ER alpha gene, and this is required for RNA polymerase II recruitment to ER alpha promoters. Reciprocally, ER alpha directly stimulates the transcription of the GATA-3 gene, indicating that these two factors are involved in a positive cross-regulatory loop. Moreover, GATA-3 and ER alpha regulate their own expression in breast cancer cells. Hence, this transcriptional coregulatory mechanism accounts for the robust coexpression of GATA-3 and ER alpha in human breast cancers. In addition, these results highlight the crucial role of GATA-3 for the response of ER alpha-positive breast cancers to estradiol. Moreover, they identify GATA-3 as a critical component of the master cell-type-specific transcriptional network including ER alpha and FoxA1 that dictates the phenotype of hormone-dependent breast cancer.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

MeSH terms

LinkOut - more resources