Research article summary (published 13 Feb 2007):

G protein-coupled receptor 30 (GPR30) mediates gene expression changes and growth response to 17beta-estradiol and selective GPR30 ligand G-1 in ovarian cancer cells.

Full Abstract

Estrogens play a crucial role in the development of ovarian tumors; however, the signal transduction pathways involved in hormone action are still poorly defined. The orphan G protein-coupled receptor 30 (GPR30) mediates the nongenomic signaling of 17beta-estradiol (E2) in a variety of estrogen-sensitive cancer cells through activation of the epidermal growth factor receptor (EGFR) pathway. Whether estrogen receptor alpha (ERalpha) also contributes to GPR30/EGFR signaling is less understood. Here, we show that, in ERalpha-positive BG-1 ovarian cancer cells, both E2 and the GPR30-selective ligand G-1 induced c-fos expression and estrogen-responsive element (ERE)-independent activity of a c-fos reporter gene, whereas only E2 stimulated an ERE-responsive reporter gene, indicating that GPR30 signaling does not activate ERalpha-mediated transcription. Similarly, both ligands up-regulated cyclin D1, cyclin E, and cyclin A, whereas only E2 enhanced progesterone receptor expression. Moreover, both GPR30 and ERalpha expression are required for c-fos stimulation and extracellular signal-regulated kinase (ERK) activation in response to either E2 or G-1. Inhibition of the EGFR transduction pathway inhibited c-fos stimulation and ERK activation by either ligand, suggesting that in ovarian cancer cells GPR30/EGFR signaling relays on ERalpha expression. Interestingly, we show that both GPR30 and ERalpha expression along with active EGFR signaling are required for E2-stimulated and G-1-stimulated proliferation of ovarian cancer cells. Because G-1 was able to induce both c-fos expression and proliferation in the ERalpha-negative/GPR30-positive SKBR3 breast cancer cells, the requirement for ERalpha expression in GPR30/EGFR signaling may depend on the specific cellular context of different tumor types.

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Author information

Author/s: Albanito, Lidia (L); Madeo, Antonio (A); Lappano, Rosamaria (R); Vivacqua, Adele (A); Rago, Vittoria (V); Carpino, Amalia (A); Oprea, Tudor I (TI); Prossnitz, Eric R (ER); Musti, Anna Maria (AM); Andò, Sebastiano (S); Maggiolini, Marcello (M);

Affiliation: Departments of Pharmaco-Biology and Cell Biology, University of Calabria, 87030 Rende (Cosenza), Italy.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: Cancer research (Cancer Res), published in United States. (Language: eng)

Reference: 2007-Feb; vol 67 (issue 4) : pp 1859-66

Dates: Created 2007/02/19; Completed 2007/03/15; Revised 2008/11/21;

PMID: 17308128, status: MEDLINE (last retrieval date: 12/26/2008)

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Breast Neoplasms - genetics; metabolism; pathology Cell Growth Processes Cell Line, Tumor Cyclopentanes - pharmacology Estradiol - pharmacology Estrogen Receptor alpha - metabolism Female Gene Expression Regulation, Neoplastic

Genes, fos Humans Ovarian Neoplasms - genetics; metabolism; pathology Promoter Regions, Genetic Proto-Oncogene Proteins c-fos - biosynthesis; genetics Quinolines - pharmacology RNA, Messenger - biosynthesis; genetics Receptors, G-Protein-Coupled - metabolism; physiology Signal Transduction

Associated Chemicals: 1-(4-(6-bromobenzo(1,3)dioxol-5-yl)-3a,4,5,9b-tetrahydro-3H-cyclopenta(c)quinolin-8-yl)ethanone (0) ; Cyclopentanes (0) ; Estrogen Receptor alpha (0) ; GPER protein, human (0) ; Proto-Oncogene Proteins c-fos (0) ; Quinolines (0) ; RNA, Messenger (0) ; Receptors, G-Protein-Coupled (0) ; Estradiol (50-28-2)

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