@article {29991,
	title = {Evaluation of the coordinated actions of estrogen receptors with epidermal growth factor receptor and insulin-like growth factor receptor in the expression of cell surface heparan sulfate proteoglycans and cell motility in breast cancer cells},
	journal = {FEBS JFEBS J},
	volume = {280},
	number = {10},
	year = {2013},
	note = {Tsonis, Anastasios IAfratis, NikolaosGialeli, ChrisostomiEllina, Maria-IoannaPiperigkou, ZoiSkandalis, Spyridon STheocharis, Achilleas DTzanakakis, George NKaramanos, Nikos KengResearch Support, Non-U.S. Gov{\textquoteright}tEngland2013/02/05FEBS J. 2013 May;280(10):2248-59. doi: 10.1111/febs.12162. Epub 2013 Feb 27.},
	month = {May},
	pages = {2248-59},
	edition = {20130227},
	abstract = {Estradiol (E2)-estrogen receptor (ER) actions are implicated in initiation, growth and progression of hormone-dependent breast cancer. Crosstalk between ERs, epidermal growth factor receptor (EGFR) and/or insulin-like growth factor receptor (IGFR) is critical for the observed resistance to endocrine therapies. Cell surface heparan sulfate proteoglycans (HSPGs) are principal mediators of cancer cell properties and the E2-ER pathway as well as those activated by EGFR and IGFR have significant roles in regulating the expression of certain cell surface HSPGs, such as syndecan-2 (SDC-2), syndecan-4 (SDC-4) and glypican-1. In this study, we therefore evaluated the role of EGFR-IGFR signaling on the constitutive expression and E2-mediated expression of ERs and HSPGs as well as the effect of E2-ERs and IGFR/EGFR-mediated cell migration in ERalpha+ (MCF-7) and ERbeta+ (MDA-MB-231) breast cancer cells using specific intracellular inhibitors of EGFR and IGFR. We report that the expression of ERalpha is mainly enhanced by IGFR, whereas ERbeta expression is mainly coordinated by EGFR. Moreover, constitutive SDC-2 expression in ERalpha+ and ERbeta+ cells is mainly mediated through the IGFR, whereas in ERalpha+ E2-treated cells EGFR is the active one. In contrast, SDC-4 expression is regulated by IGFR in the presence and absence of E2. E2 also seems to diminish the inhibitory effect of EGFR and IGFR inhibitors in breast cancer cell migration. These data suggest that the coordinated action of ERs with EGFR and/or IGFR is of crucial importance, providing potential targets for designing and developing novel multi-potent agents for endocrine therapies.},
	keywords = {Breast Neoplasms/metabolism/pathology, Cell Movement/*drug effects, ErbB Receptors/antagonists \& inhibitors/*metabolism, Estradiol/*metabolism/pharmacology, Estrogen Receptor alpha/genetics/*metabolism, Estrogen Receptor beta/genetics/metabolism, Female, Gene Expression Regulation, Glypicans/genetics/metabolism, Humans, Insulin-Like Growth Factor I/antagonists \& inhibitors/*metabolism, MCF-7 Cells, Quinazolines/pharmacology, Receptor Cross-Talk, signal transduction, Syndecan-2/genetics/*metabolism, Syndecan-4/genetics/metabolism, Tyrphostins/pharmacology},
	isbn = {1742-4658 (Electronic)1742-464X (Linking)},
	author = {Tsonis, A. I. and Afratis, N. and Gialeli, C. and Ellina, M. I. and Piperigkou, Z. and Skandalis, S. S. and Theocharis, A. D. and Tzanakakis, G. N. and Karamanos, N. K.}
}
