| First Author | Wu WF | Year | 2021 |
| Journal | Proc Natl Acad Sci U S A | Volume | 118 |
| Issue | 13 | PubMed ID | 33771918 |
| Mgi Jnum | J:304008 | Mgi Id | MGI:6681981 |
| Doi | 10.1073/pnas.2011269118 | Citation | Wu WF, et al. (2021) Estrogen receptor beta and treatment with a phytoestrogen are associated with inhibition of nuclear translocation of EGFR in the prostate. Proc Natl Acad Sci U S A 118(13):e2011269118 |
| abstractText | Knockout of ERbeta in the mouse leads to nuclear expression of epidermal growth factor receptor (EGFR) in the prostate. To examine whether ERbeta 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 5alpha-reductase inhibitor, finasteride, and finasteride together with the ERbeta 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 ERbeta 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 ERbeta expression, but, on treatment longer than 8 mo, ERbeta was lost and EGFR moved to the nucleus. Since nuclear EGFR is a predictor of poor outcome in PCa, addition of ERbeta agonists together with abiraterone should be considered as a treatment that might sustain expression of ERbeta and offer some benefit to patients. |
