H-ras Dependent Estrogenic Effects of Epidermal Growth Factor in the Estrogen-Independent Breast Cancer Cell Line MDA-MB-231

Authors: Treeck O.¹; Weber A.²; Boester M.²; Porz S.²; Frey N.²; Diedrich K.²; Ortmann O.¹

Source: Breast Cancer Research and Treatment, Volume 80, Number 2, July 2003 , pp. 155-162(8)

Publisher: Springer

Abstract:

A crosstalk between cellular estrogen response and receptor tyrosine kinase signaling has been shown in a variety of estrogen receptor (ER)-positive cell lines. We intended to examine the presence of estrogenic growth factor effects in an ER -negative breast cancer cell line. By means of reporter gene assays, we investigated the activation of estrogen response elements (EREs) by epidermal growth factor (EGF) in the estrogen-unresponsive cell line MDA-MB-231. Our results demonstrate the H-ras-dependent activation of EREs after EGF treatment in this estrogen-unresponsive cell line, an effect which was not observed in the ER/-positive breast cancer cell line MCF-7. In MDA-MB-231 cells, the transcriptional activity of an ERE-containing promotor was enhanced dose dependently by all tested EGF concentrations. This effect could be blocked by co-treatment with the epidermal growth factor receptor (EGFR) inhibitors AG1478 and ZD1839, as well as by co-transfection with a vector coding for a dominant negative H-ras mutant, but not by co-treatment with the pure antiestrogen ICI182,780. Furthermore, expression of constitutively active H-ras was shown to be sufficient to activate EREs in MDA-MB-231 cells. Our results suggest alternative utilization of ERE-mediated gene regulation in an estradiol-unresponsive breast cancer cell line in response to an EGF stimulus. This mechanism was shown to be dependent on EGFR and H-ras activity, but independent of the presence of functional ER.

Keywords: epidermal growth factor; estrogen receptor; estrogen response element; H-ras; MDA-MB-231 cell

Language: English

Document Type: Research article

Affiliations: 1: Department of Obstetrics and Gynecology, University of Regensburg, Regensburg, Germany 2: Department of Obstetrics and Gynecology, Medical University of Lübeck, Lübeck, Germany

Publication date: 2003-07-01

• In this: publication
• By this: publisher
• In this Subject: Obstetrics & Gynecology ,  Oncology
• By this author: Treeck O. ;  Weber A. ;  Boester M. ;  Porz S. ;  Frey N. ;  Diedrich K. ;  Ortmann O.

Website © Publishing Technology. Article copyright remains with the publisher, society or author(s) as specified within the article.

• Terms and conditions
• Privacy policy
• Information for advertisers