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GPER and Testicular Germ Cell Cancer.
Nicolas Chevalier1,2, Charlotte Hinault1,2, Stephan Clavel2
1Université Côte d'Azur, CHU, INSERM U1065, C3M, Nice, France.
Frontiers in Endocrinology
|February 12, 2021
Summary
The G protein-coupled estrogen receptor (GPER) is overexpressed in testicular germ cell cancers (TGCCs), unlike classic estrogen receptors. This suggests GPER may be a therapeutic target for male reproductive cancers.
Area of Science:
- Endocrinology
- Oncology
- Molecular Biology
Background:
- The G protein-coupled estrogen receptor (GPER), also known as GPR30, is a novel estrogen-binding protein distinct from ERα and ERβ.
- Conflicting data exist on GPER's role in reproductive tracts, as knockout mice show normal fertility.
- Testicular germ cell cancers (TGCCs) are common in young males, and estrogens are implicated in germ cell proliferation.
Purpose of the Study:
- To investigate the role of GPER/GPR30 in the pathophysiology of TGCCs.
- To explore GPER/GPR30 as a potential therapeutic target for TGCCs.
Main Methods:
- Utilized human seminoma cell lines and investigated the effects of 17β-estradiol (E2) and an impermeable E2 conjugate.
- Examined the activation of signaling pathways (ERK1/2, protein kinase A) and GPER/GPR30 expression in cancer cells.
- Analyzed GPER/GPR30 expression in seminomas versus non-seminomas and correlated it with ERβ levels.
Main Results:
- 17β-estradiol (E2) inhibits seminoma cell proliferation via ERβ, while an impermeable E2 conjugate stimulates proliferation through GPER/GPR30 activation of ERK1/2 and protein kinase A.
- Environmentally relevant doses of Bisphenol A (BPA) mimicked the proliferative effect of GPER/GPR30 activation.
- GPER/GPR30 is specifically overexpressed in seminomas, not non-seminomas, and this is associated with ERβ downregulation.
- GPER/GPR30 overexpression may be linked to genetic variations like single nucleotide polymorphisms.
Conclusions:
- GPER/GPR30 plays a distinct role in TGCC pathophysiology compared to classical estrogen receptors.
- GPER/GPR30 is a potential therapeutic target for seminomas.
- Further research into GPER/GPR30's role and genetic variations in hormone-dependent cancers is warranted.
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