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Cited by 160Prostate Cancer Treatment and ResearchProtein Kinase Regulation and GTPase SignalingEstrogen and related hormone effects

A Rapid, Nongenomic, Signaling Pathway Regulates the Actin Reorganization Induced by Activation of Membrane Testosterone Receptors

Papakonstanti, Evangelia A., Kampa, Marilena, Castanas, Elias, Stournaras, Christos·2003·Molecular Endocrinology
DOI 10.1210/me.2002-0253
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Abstract

The human prostate cancer cell line LNCaP bears functional membrane testosterone receptors, which modify the actin cytoskeleton and increase the secretion of prostate-specific antigen (PSA) within minutes. Membrane steroid receptors are, indeed, a newly identified element of steroid action that is different from the classical intracellular sites. In the present work, using a nonpermeable analog of testosterone (testosterone-BSA), we investigated the signaling pathway that is triggered by the membrane testosterone receptors' activation and leads to actin cytoskeleton reorganization. We report that exposure of cells to testosterone-BSA resulted in phosphorylation of focal adhesion kinase (FAK), the association of FAK with the phosphatidylinositol-3 (PI-3) kinase, and the subsequent activation of the latter as well as the activation of the small guanosine triphosphatases Cdc42/Rac1. Pretreatment of cells with the specific PI-3 kinase inhibitor wortmannin abolished both the activation of the small guanosine triphosphatases and the alterations of actin cytoskeleton, whereas it did not affect the phosphorylation of FAK. These findings indicate that PI-3 kinase is activated downstream of FAK and upstream of Cdc42/Rac1, which subsequently regulate the actin organization. Moreover, wortmannin diminished the secretion of PSA, implying that the signaling events described above are responsible for the testosterone-BSA-induced PSA secretion. Our results are discussed under the prism of a possible implication of these membrane receptors in prostate cancer chemotherapy.

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  • Androgen receptors can be modulated by specific proteins called coregulators or mediated via activation of membrane-bound protein receptors to initiate intracellular signalling pathways, which can occur even in the presence of low levels of androgens.

    “Androgen receptors can be modulated by specific proteins called coregulators [70–72] or mediated via the activation of membrane-bound protein receptors to initiate intracellular signalling pathways [73], which can occur even in the presence of low levels of androgens [74].”

    From Integrating Transwomen and Female Athletes with Differences of Sex Development (DSD) into Elite Competition: The FIMS 2021 Consensus Statement (2021) · cites this paper as [73]

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Authors
Papakonstanti, E. A., Kampa, M., Castanas, E., & Stournaras, C.
Affiliations
University of Crete (GR)
Corresponding author
Stournaras, Christos
ORCID
Venue
Molecular Endocrinology
Publisher
The Endocrine Society
Published
2003-05
Volume
17
Issue
5
Pages
870-881
ISSN
  • 0888-8809 (ISSN-L)
  • 1944-9917
DOI
10.1210/me.2002-0253
OpenAlex
W2059939225
Cited by
160
References
74
Citations by year
2026: 3 · 2025: 3 · 2024: 4 · 2023: 7 · 2022: 3 · 2021: 4 · 2020: 3 · 2019: 6 · 2018: 4 · 2017: 11 · 2016: 4 · 2015: 2 · 2014: 10 · 2013: 7 · 2012: 6
FWCI
8.10
Type
journal article
Language
en
Open access
closed
Locations
  • Molecular Endocrinology (publishedVersion)
  • PubMed (publishedVersion)
Funders
Olympus
Topics
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Prostate Cancer Treatment and Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Estrogen and related hormone effects
Keywords
non-genomic steroid action, actin cytoskeleton remodeling, focal adhesion kinase, phosphatidylinositol 3-kinase, Cdc42, Rac1, small GTPases, prostate-specific antigen secretion, wortmannin, prostate cancer, LNCaP cells
MeSH terms
Wortmannin, Phosphoinositide-3 Kinase Inhibitors, Actins, Androstadienes, Cell Membrane, Cytoskeleton, Enzyme Inhibitors, Humans, Male, Neuropeptides, Phosphorylation, Prostatic Neoplasms, Protein-Tyrosine Kinases, Receptors, Androgen, Serum Albumin, Bovine, Dihydrotestosterone, Testosterone, Tumor Cells, Cultured, Signal Transduction, Prostate-Specific Antigen, Phosphatidylinositol 3-Kinases, rac GTP-Binding Proteins, cdc42 GTP-Binding Protein, rac1 GTP-Binding Protein, Focal Adhesion Protein-Tyrosine Kinases, Focal Adhesion Kinase 1

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