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The evolving role of oestrogens and their receptors in the development and progression of prostate cancer
European Urology, 02/11/09

Bonkhoff H et al. - In a study to examine mechanisms of how oestrogens may affect prostate carcinogenesis and tumour progression, it was shown that oestrogens and their receptors, oestrogen receptor alpha (ERα) and oestrogen receptor beta (ERβ), are involved in prostate carcinogenesis and tumour progression, and they represent potential targets for prostate cancer prevention and treatment.

Methods

Recent data obtained from animal, experimental, and clinical studies were reviewed.

Results

The human prostate is equipped with a dual system of oestrogen receptors (oestrogen receptor alpha [ERα], oestrogen receptor beta [ERβ]) that undergoes profound remodelling during PCa development and tumour progression.
In high-grade prostatic intraepithelial neoplasia (HGPIN), ERα is upregulated and most likely mediates carcinogenic effects of estradiol as demonstrated in animal models.
Preliminary clinical studies with the ERα antagonist toremifene have identified ERα as a promising target for PCa prevention.
Partial loss of the ERβ in HGPIN indicates that the ERβ acts as a tumour suppressor.
ERβ is generally retained in hormone-naïve PCa but is partially lost in castration-resistant disease.
Progressive emergence of the ERα and oestrogen-regulated progesterone receptor (PR) during PCa progression and hormone-refractory disease suggests that these tumours can use oestrogens and progestins for their growth.
TMPRSS2-ERG gene fusion, recently reported as a potentially aggressive molecular subtype of PCa, is regulated by ER-dependent signalling.
TMPRSS2-ERG expression has been found to be increased by ERα agonist (oestrogens) and decreased by ERβ agonists.

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