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Estrogen receptor ß and treatment with a phytoestrogen are associated with inhibition of nuclear translocation of EGFR in the prostate.
Wu, Wan-Fu; Wang, Li; Spetsieris, Nicholas; Boukovala, Myrto; Efstathiou, Eleni; Brössner, Clemens; Warner, Margaret; Gustafsson, Jan-Ake.
Afiliação
  • Wu WF; Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204.
  • Wang L; Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204.
  • Spetsieris N; Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
  • Boukovala M; Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
  • Efstathiou E; Department of Genitourinary Medical Oncology, University of Texas MD Anderson Cancer Center, Houston, TX 77030.
  • Brössner C; Department of Urology, Barmherzige Schwestern Hospital, 1060 Vienna, Austria.
  • Warner M; Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204.
  • Gustafsson JA; Center for Nuclear Receptors and Cell Signaling, Department of Biology and Biochemistry, University of Houston, Houston, TX 77204; jgustafsson@uh.edu.
Proc Natl Acad Sci U S A ; 118(13)2021 03 30.
Article em En | MEDLINE | ID: mdl-33771918
ABSTRACT
Knockout of ERß in the mouse leads to nuclear expression of epidermal growth factor receptor (EGFR) in the prostate. To examine whether ERß plays a similar role in the human prostate, we used four cohorts of men 1) a Swedish cohort of normal prostates and PCa (prostate cancer) of different Gleason grades; 2) men with benign prostatic hyperplasia (BPH) treated with the 5α-reductase inhibitor, finasteride, and finasteride together with the ERß agonists, soy isoflavones; 3) men with PCa above Gleason grade 4 (GG4), treated with ADT (androgen deprivation therapy) and abiraterone (AA), the blocker of androgen synthesis for different durations; and 4) men with GG4 PCa on ADT or ADT with the AR (androgen receptor) blocker, enzalutamide, for 4 mo to 6 mo. In men with BPH, finasteride treatment induced EGFR nuclear expression, but, when finasteride was combined with isoflavones, EGFR remained on the cell membrane. In GG4 patients, blocking of AR for 4 mo to 6 mo resulted in loss of ERß and PTEN expression and increase in patients with nuclear EGFR from 10 to 40%. In the men with GG4 PCa, blocking of adrenal synthesis of testosterone for 2 mo to 7 mo had the beneficial effect of increasing ERß expression, but, on treatment longer than 8 mo, ERß was lost and EGFR moved to the nucleus. Since nuclear EGFR is a predictor of poor outcome in PCa, addition of ERß agonists together with abiraterone should be considered as a treatment that might sustain expression of ERß and offer some benefit to patients.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hiperplasia Prostática / Neoplasias da Próstata / Protocolos de Quimioterapia Combinada Antineoplásica / Receptor beta de Estrogênio Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Hiperplasia Prostática / Neoplasias da Próstata / Protocolos de Quimioterapia Combinada Antineoplásica / Receptor beta de Estrogênio Tipo de estudo: Etiology_studies / Incidence_studies / Observational_studies / Prognostic_studies / Risk_factors_studies Idioma: En Revista: Proc Natl Acad Sci U S A Ano de publicação: 2021 Tipo de documento: Article