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Updated: Jan 30, 2026

A Bioluminescent and Fluorescent Orthotopic Syngeneic Murine Model of Androgen-dependent and Castration-resistant Prostate Cancer
Published on: March 6, 2018
Membrane androgen receptors (OXER1, GPRC6A AND ZIP9) in prostate and breast cancer: A comparative study of their
Konstantina Kalyvianaki1, Athanasios A Panagiotopoulos1, Panagiotis Malamos1
1Laboratory of Experimental Endocrinology, University of Crete, School of Medicine, Heraklion 71013, Greece.
Abstract:
Accumulating evidence during the last decades revealed that androgens exert membrane-initiated actions leading to the modulation of significant cellular processes, important for cancer cell growth and metastasis (including prostate and breast), that involve signaling via specific kinases. Collectively, many nonclassical, cell surface-initiated androgen actions are mediated by novel membrane androgen receptors (mARs), unrelated to nuclear androgen receptors. Recently, our group identified the G protein coupled oxo-eicosanoid receptor 1 (OXER1) (a receptor of the arachidonic acid metabolite, 5-oxoeicosatetraenoic acid, 5-oxoETE) as a novel mAR involved in the rapid effects of androgens. However, two other membrane proteins, G protein-coupled receptor family C group 6 member A (GPRC6A) and zinc transporter member 9 (ZIP9) have also been portrayed as mARs, related to the extranuclear action of androgens. In the present work, we present a comparative study of in silico pharmacology, gene expression and immunocytochemical data of the three receptors in various prostate and breast cancer cell lines. Furthermore, we analyzed the immunohistochemical expression of these receptors in human tumor and non-tumoral specimens and provide a pattern of expression and intracellular distribution.
Insights
This study compares three membrane androgen receptors (mARs) – OXER1, GPRC6A, and ZIP9 – in prostate and breast cancers. Findings reveal distinct expression patterns, aiding understanding of nonclassical androgen actions in cancer progression.
Area of Science:
- Oncology
- Cell Biology
- Molecular Endocrinology
Background:
- Androgens regulate cellular processes via membrane-initiated actions, distinct from nuclear receptors.
- Novel membrane androgen receptors (mARs) mediate these nonclassical, rapid androgen effects.
- OXER1, GPRC6A, and ZIP9 are identified as potential mARs involved in cancer.
Purpose of the Study:
- To comparatively analyze OXER1, GPRC6A, and ZIP9 as mARs in prostate and breast cancer.
- To investigate their in silico pharmacology, gene expression, and immunocytochemical profiles.
- To determine their expression patterns and intracellular distribution in human tumor tissues.
Main Methods:
- In silico pharmacology analysis.
- Gene expression profiling.
- Immunocytochemistry and immunohistochemistry on cell lines and human tissue specimens.
Main Results:
- Comparative analysis of OXER1, GPRC6A, and ZIP9 expression and distribution in cancer cell lines.
- Immunohistochemical evaluation of these mARs in human prostate and breast tumors versus non-tumoral tissues.
- Identification of specific expression patterns and subcellular localization for each receptor.
Conclusions:
- OXER1, GPRC6A, and ZIP9 exhibit distinct expression profiles in prostate and breast cancers.
- These mARs show varied intracellular localization, suggesting diverse functional roles.
- Understanding these mARs is crucial for targeting nonclassical androgen signaling in cancer therapy.
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