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

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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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Authors: Papakonstanti, E. A., Kampa, M., Castanas, E., & Stournaras, C.
Affiliations: University of Crete (GR)
Corresponding author: Stournaras, Christos
ORCID: Papakonstanti, Evangelia A.
Kampa, Marilena
Castanas, Elias
Stournaras, Christos
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: Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › 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 › Endocrinology › 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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A Rapid, Nongenomic, Signaling Pathway Regulates the Actin Reorganization Induced by Activation of Membrane Testosterone Receptors

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