Androgen receptor is causally involved in the homeostasis of the human prostate endothelial cell

Alejandro Godoy, Anica Watts, Paula Sotomayor, Viviana P. Montecinos, Wendy J. Huss, Sergio A. Onate, Gary J. Smith

Resultado de la investigación: Article

28 Citas (Scopus)

Resumen

Androgen deprivation causes a reduction of blood flow in the prostate gland that precedes temporally apoptosis of the epithelium. The acute response of prostate endothelial cells to androgen deprivation suggested they represent a primary target for androgen. However, rat prostate endothelial cells were reported not to express androgen receptor (AR), and the role of the androgen axis in human prostate endothelial cell (HPEC) homeostasis was poorly characterized. In this study AR expression was detected in HPEC in vivo in clinical specimens of benign prostate and prostate cancer, and AR function as a transcription factor was demonstrated in HPEC in primary xenografts of human benign prostate tissue transplanted into severe combined immunodeficient mice by iv administration of adenoviral mouse mammary tumor virusdriven luciferase expression vector. AR expression and functionality were maintained in vitro in primary cultures of HPEC that coexpressed CD31, CD34, von Willebrand factor, intercellular adhesion molecule, vascular endothelial growth factor receptor 1, and vascular endothelial growth factor receptor 2 but did not express prostate-specific antigen. AR expression in primary cultures of HPEC isolated from surgical specimens of benign prostate was validated using RT-PCR, cDNA sequencing, immunocytochemistry, and Western blot analyses. Scatchard analyses demonstrated a single ligand-binding site for R1881 in primary cultures of HPEC, with dissociation constant of 0.25 nM, and AR-mediated transcriptional activity was demonstrated using adenoviral mouse mammary tumor virus-driven luciferase reporters. Dihydrotestosterone increased proliferation in primary cultures of HPEC in a dose-dependent manner without modulating endothelial tube formation in Matrigel (BD Biosciences, Bedford, MA). Therefore, HPECs express functional AR, and androgen plays a direct role in modulating HPEC biology.

Idioma originalEnglish
Páginas (desde-hasta)2959-2969
Número de páginas11
PublicaciónEndocrinology
Volumen149
N.º6
DOI
EstadoPublished - jun 2008

Huella dactilar

Androgen Receptors
Prostate
Homeostasis
Endothelial Cells
Androgens
Luciferases
Metribolone
Mouse mammary tumor virus
Vascular Endothelial Growth Factor Receptor-1
Vascular Endothelial Growth Factor Receptor-2
SCID Mice
Dihydrotestosterone
von Willebrand Factor
Cell Adhesion Molecules
Prostate-Specific Antigen
Heterografts
Cell Biology
Prostatic Neoplasms
Transcription Factors
Epithelium

ASJC Scopus subject areas

  • Endocrinology
  • Endocrinology, Diabetes and Metabolism

Citar esto

Godoy, A., Watts, A., Sotomayor, P., Montecinos, V. P., Huss, W. J., Onate, S. A., & Smith, G. J. (2008). Androgen receptor is causally involved in the homeostasis of the human prostate endothelial cell. Endocrinology, 149(6), 2959-2969. https://doi.org/10.1210/en.2007-1078
Godoy, Alejandro ; Watts, Anica ; Sotomayor, Paula ; Montecinos, Viviana P. ; Huss, Wendy J. ; Onate, Sergio A. ; Smith, Gary J. / Androgen receptor is causally involved in the homeostasis of the human prostate endothelial cell. En: Endocrinology. 2008 ; Vol. 149, N.º 6. pp. 2959-2969.
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abstract = "Androgen deprivation causes a reduction of blood flow in the prostate gland that precedes temporally apoptosis of the epithelium. The acute response of prostate endothelial cells to androgen deprivation suggested they represent a primary target for androgen. However, rat prostate endothelial cells were reported not to express androgen receptor (AR), and the role of the androgen axis in human prostate endothelial cell (HPEC) homeostasis was poorly characterized. In this study AR expression was detected in HPEC in vivo in clinical specimens of benign prostate and prostate cancer, and AR function as a transcription factor was demonstrated in HPEC in primary xenografts of human benign prostate tissue transplanted into severe combined immunodeficient mice by iv administration of adenoviral mouse mammary tumor virusdriven luciferase expression vector. AR expression and functionality were maintained in vitro in primary cultures of HPEC that coexpressed CD31, CD34, von Willebrand factor, intercellular adhesion molecule, vascular endothelial growth factor receptor 1, and vascular endothelial growth factor receptor 2 but did not express prostate-specific antigen. AR expression in primary cultures of HPEC isolated from surgical specimens of benign prostate was validated using RT-PCR, cDNA sequencing, immunocytochemistry, and Western blot analyses. Scatchard analyses demonstrated a single ligand-binding site for R1881 in primary cultures of HPEC, with dissociation constant of 0.25 nM, and AR-mediated transcriptional activity was demonstrated using adenoviral mouse mammary tumor virus-driven luciferase reporters. Dihydrotestosterone increased proliferation in primary cultures of HPEC in a dose-dependent manner without modulating endothelial tube formation in Matrigel (BD Biosciences, Bedford, MA). Therefore, HPECs express functional AR, and androgen plays a direct role in modulating HPEC biology.",
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Godoy, A, Watts, A, Sotomayor, P, Montecinos, VP, Huss, WJ, Onate, SA & Smith, GJ 2008, 'Androgen receptor is causally involved in the homeostasis of the human prostate endothelial cell', Endocrinology, vol. 149, n.º 6, pp. 2959-2969. https://doi.org/10.1210/en.2007-1078

Androgen receptor is causally involved in the homeostasis of the human prostate endothelial cell. / Godoy, Alejandro; Watts, Anica; Sotomayor, Paula; Montecinos, Viviana P.; Huss, Wendy J.; Onate, Sergio A.; Smith, Gary J.

En: Endocrinology, Vol. 149, N.º 6, 06.2008, p. 2959-2969.

Resultado de la investigación: Article

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AU - Godoy, Alejandro

AU - Watts, Anica

AU - Sotomayor, Paula

AU - Montecinos, Viviana P.

AU - Huss, Wendy J.

AU - Onate, Sergio A.

AU - Smith, Gary J.

PY - 2008/6

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N2 - Androgen deprivation causes a reduction of blood flow in the prostate gland that precedes temporally apoptosis of the epithelium. The acute response of prostate endothelial cells to androgen deprivation suggested they represent a primary target for androgen. However, rat prostate endothelial cells were reported not to express androgen receptor (AR), and the role of the androgen axis in human prostate endothelial cell (HPEC) homeostasis was poorly characterized. In this study AR expression was detected in HPEC in vivo in clinical specimens of benign prostate and prostate cancer, and AR function as a transcription factor was demonstrated in HPEC in primary xenografts of human benign prostate tissue transplanted into severe combined immunodeficient mice by iv administration of adenoviral mouse mammary tumor virusdriven luciferase expression vector. AR expression and functionality were maintained in vitro in primary cultures of HPEC that coexpressed CD31, CD34, von Willebrand factor, intercellular adhesion molecule, vascular endothelial growth factor receptor 1, and vascular endothelial growth factor receptor 2 but did not express prostate-specific antigen. AR expression in primary cultures of HPEC isolated from surgical specimens of benign prostate was validated using RT-PCR, cDNA sequencing, immunocytochemistry, and Western blot analyses. Scatchard analyses demonstrated a single ligand-binding site for R1881 in primary cultures of HPEC, with dissociation constant of 0.25 nM, and AR-mediated transcriptional activity was demonstrated using adenoviral mouse mammary tumor virus-driven luciferase reporters. Dihydrotestosterone increased proliferation in primary cultures of HPEC in a dose-dependent manner without modulating endothelial tube formation in Matrigel (BD Biosciences, Bedford, MA). Therefore, HPECs express functional AR, and androgen plays a direct role in modulating HPEC biology.

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Godoy A, Watts A, Sotomayor P, Montecinos VP, Huss WJ, Onate SA y otros. Androgen receptor is causally involved in the homeostasis of the human prostate endothelial cell. Endocrinology. 2008 jun;149(6):2959-2969. https://doi.org/10.1210/en.2007-1078