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G Protein-Coupled Estrogen Receptor-Selective Ligands Modulate Endometrial Tumor Growth
Joint Authors
Arterburn, Jeffrey B.
Hu, Chelin
Hathaway, Helen J.
Petrie, Whitney K.
Dai, Donghai D.
Dennis, Megan K.
Prossnitz, Eric R.
Smith, Harriet O.
Source
Obstetrics and Gynecology International
Issue
Vol. 2013, Issue 2013 (31 Dec. 2013), pp.1-17, 17 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2013-11-27
Country of Publication
Egypt
No. of Pages
17
Main Subjects
Abstract EN
Endometrial carcinoma is the most common cancer of the female reproductive tract.
GPER/GPR30 is a 7-transmembrane spanning G protein-coupled receptor that has been identified as the third estrogen receptor, in addition to ERα and ERβ.
High GPER expression is predictive of poor survival in endometrial and ovarian cancer, but despite this, the estrogen-mediated signaling pathways and specific estrogen receptors involved in endometrial cancer remain unclear.
Here, employing ERα-negative Hec50 endometrial cancer cells, we demonstrate that GPER mediates estrogen-stimulated activation of ERK and PI3K via matrix metalloproteinase activation and subsequent transactivation of the EGFR and that ER-targeted therapeutic agents (4-hydroxytamoxifen, ICI182,780/fulvestrant, and Raloxifene), the phytoestrogen genistein, and the “ERα-selective” agonist propylpyrazole triol also function as GPER agonists.
Furthermore, xenograft tumors of Hec50 cells yield enhanced growth with G-1 and estrogen, the latter being inhibited by GPER-selective pharmacologic antagonism with G36.
These results have important implications with respect to the use of putatively ER-selective ligands and particularly for the widespread long-term use of “ER-targeted” therapeutics.
Moreover, our findings shed light on the potential mechanisms of SERM/SERD side effects reported in many clinical studies.
Finally, our results provide the first demonstration that pharmacological inhibition of GPER activity in vivo prevents estrogen-mediated tumor growth.
American Psychological Association (APA)
Petrie, Whitney K.& Dennis, Megan K.& Hu, Chelin& Dai, Donghai D.& Arterburn, Jeffrey B.& Smith, Harriet O.…[et al.]. 2013. G Protein-Coupled Estrogen Receptor-Selective Ligands Modulate Endometrial Tumor Growth. Obstetrics and Gynecology International،Vol. 2013, no. 2013, pp.1-17.
https://search.emarefa.net/detail/BIM-474256
Modern Language Association (MLA)
Petrie, Whitney K.…[et al.]. G Protein-Coupled Estrogen Receptor-Selective Ligands Modulate Endometrial Tumor Growth. Obstetrics and Gynecology International No. 2013 (2013), pp.1-17.
https://search.emarefa.net/detail/BIM-474256
American Medical Association (AMA)
Petrie, Whitney K.& Dennis, Megan K.& Hu, Chelin& Dai, Donghai D.& Arterburn, Jeffrey B.& Smith, Harriet O.…[et al.]. G Protein-Coupled Estrogen Receptor-Selective Ligands Modulate Endometrial Tumor Growth. Obstetrics and Gynecology International. 2013. Vol. 2013, no. 2013, pp.1-17.
https://search.emarefa.net/detail/BIM-474256
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-474256