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Impact of Androgen Receptor Activity on Prostate-Specific Membrane Antigen Expression in Prostate Cancer Cells.
Sommer, Ulrich; Siciliano, Tiziana; Ebersbach, Celina; Beier, Alicia-Marie K; Stope, Matthias B; Jöhrens, Korinna; Baretton, Gustavo B; Borkowetz, Angelika; Thomas, Christian; Erb, Holger H H.
Afiliación
  • Sommer U; Institute of Pathology, Universitätsklinikum Carl Gustav Carus Dresden, 01307 Dresden, Germany.
  • Siciliano T; Department of Urology, Technische Universität Dresden, 01307 Dresden, Germany.
  • Ebersbach C; Department of Urology, Technische Universität Dresden, 01307 Dresden, Germany.
  • Beier AK; Mildred Scheel Early Career Center, Department of Urology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.
  • Stope MB; Department of Urology, Technische Universität Dresden, 01307 Dresden, Germany.
  • Jöhrens K; Mildred Scheel Early Career Center, Department of Urology, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, 01307 Dresden, Germany.
  • Baretton GB; Department of Gynecology and Gynecological Oncology, University Hospital Bonn, 53127 Bonn, Germany.
  • Borkowetz A; UroFors Consortium (Natural Scientists in Urological Research), German Society of Urology, 14163 Berlin, Germany.
  • Thomas C; Institute of Pathology, Universitätsklinikum Carl Gustav Carus Dresden, 01307 Dresden, Germany.
  • Erb HHH; Institute of Pathology, Universitätsklinikum Carl Gustav Carus Dresden, 01307 Dresden, Germany.
Int J Mol Sci ; 23(3)2022 Jan 18.
Article en En | MEDLINE | ID: mdl-35162969
Prostate-specific membrane antigen (PSMA) is an essential molecular regulator of prostate cancer (PCa) progression coded by the FOLH1 gene. The PSMA protein has become an important factor in metastatic PCa diagnosis and radioligand therapy. However, low PSMA expression is suggested to be a resistance mechanism to PSMA-based imaging and therapy. Clinical studies revealed that androgen receptor (AR) inhibition increases PSMA expression. The mechanism has not yet been elucidated. Therefore, this study investigated the effect of activation and inhibition of androgen signaling on PSMA expression levels in vitro and compared these findings with PSMA levels in PCa patients receiving systemic therapy. To this end, LAPC4, LNCaP, and C4-2 PCa cells were treated with various concentrations of the synthetic androgen R1881 and antiandrogens. Changes in FOLH1 mRNA were determined using qPCR. Open access databases were used for ChIP-Seq and tissue expression analysis. Changes in PSMA protein were determined using western blot. For PSMA staining in patients' specimens, immunohistochemistry (IHC) was performed. Results revealed that treatment with the synthetic androgen R1881 led to decreased FOLH1 mRNA and PSMA protein. This effect was partially reversed by antiandrogen treatment. However, AR ChIP-Seq analysis revealed no canonical AR binding sites in the regulatory elements of the FOLH1 gene. IHC analysis indicated that androgen deprivation only resulted in increased PSMA expression in patients with low PSMA levels. The data demonstrate that AR activation and inhibition affects PSMA protein levels via a possible non-canonical mechanism. Moreover, analysis of PCa tissue reveals that low PSMA expression rates may be mandatory to increase PSMA by androgen deprivation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Receptores Androgénicos / Biomarcadores de Tumor / Glutamato Carboxipeptidasa II / Antígenos de Superficie Tipo de estudio: Diagnostic_studies / Screening_studies Límite: Humans / Male Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza
Texto completo
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XML
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Neoplasias de la Próstata / Receptores Androgénicos / Biomarcadores de Tumor / Glutamato Carboxipeptidasa II / Antígenos de Superficie Tipo de estudio: Diagnostic_studies / Screening_studies Límite: Humans / Male Idioma: En Revista: Int J Mol Sci Año: 2022 Tipo del documento: Article País de afiliación: Alemania Pais de publicación: Suiza