Journal article
Epidermal growth factor receptor (EGFR) transactivation by estrogen via the G-protein-coupled receptor, GPR30: a novel signaling pathway with potential significance for breast cancer
The Journal of steroid biochemistry and molecular biology, Vol.80(2), pp.231-238
2002
DOI: 10.1016/S0960-0760(01)00190-X
PMID: 11897506
Abstract
The biological and biochemical effects of estrogen have been ascribed to its known receptors, which function as ligand-inducible transcription factors. However, estrogen also triggers rapid activation of classical second messengers (cAMP, calcium, and inositol triphosphate) and stimulation of intracellular signaling cascades mitogen-activated protein kinase (MAP K), PI3K and eNOS. These latter events are commonly activated by membrane receptors that either possess intrinsic tyrosine kinase activity or couple to heterotrimeric G-proteins. We have shown that estrogen transactivates the epidermal growth factor receptor (EGFR) to MAP K signaling axis via the G-protein-coupled receptor (GPCR), GPR30, through the release of surface-bound proHB-EGF from estrogen receptor (ER)-negative human breast cancer cells [Molecular Endocrinology 14 (2000) 1649]. This finding is consistent with a growing body of evidence suggesting that transactivation of EGFRs by GPCRs is a recurrent theme in cell signaling. GPCR-mediated transactivation of EGFRs by estrogen provides a previously unappreciated mechanism of cross-talk between estrogen and serum growth factors, and explains prior data reporting the EGF-like effects of estrogen. This novel mechanism by which estrogen activates growth factor-dependent signaling and its implications for breast cancer biology are discussed further in this review.
Details
- Title: Subtitle
- Epidermal growth factor receptor (EGFR) transactivation by estrogen via the G-protein-coupled receptor, GPR30: a novel signaling pathway with potential significance for breast cancer
- Creators
- Edward J Filardo - Department of Medicine, Division of Clinical Pharmacology, Rhode Island Hospital and Brown University, Aldrich Bldg Rm 718, 593 Eddy Street, Providence, RI 02903, USA
- Resource Type
- Journal article
- Publication Details
- The Journal of steroid biochemistry and molecular biology, Vol.80(2), pp.231-238
- Publisher
- Elsevier Ltd
- DOI
- 10.1016/S0960-0760(01)00190-X
- PMID
- 11897506
- ISSN
- 0960-0760
- eISSN
- 1879-1220
- Language
- English
- Date published
- 2002
- Academic Unit
- Pharmaceutical Sciences and Experimental Therapeutics; Surgery; Internal Medicine
- Record Identifier
- 9984051977702771
Metrics
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