Estrogen receptor gene expression and its relation to the estrogen-inducible HSP27 heat shock protein in hormone refractory prostate cancer.

Abstract

The recent discovery of the classical estrogen receptor alpha (ERalpha) in androgen-insensitive prostate cancer has shed new light on the role of estrogens in endocrine therapy failure. To get more information on downstream events of estrogen signaling in these tumors, we investigated the relation between ERalpha gene expression, and the estrogen-inducible heat shock protein HSP27 in recurrent prostatic adenocarcinomas. Palliative transurethral resection specimens from 50 patients with androgen-insensitive disease were submitted for study. Messenger RNA in situ hybridization for the ERalpha and immunohistochemistry of the HSP27 protein were performed on adjacent sections of an equal number of prostate cancer tissue with and without ERalpha protein expression. Cancerous lesions lacking the nuclear ERalpha at the protein level revealed ERalpha mRNA expression in 15 of 25 cases (60%). A coordinate expression of ERalpha mRNA and HSP27 was observed in 33 of 40 cases (83%), although a significant correlation between ERalpha protein and HSP27 expression was not obtained. Conversely, 90% of neoplastic lesions without detectable levels of ERalpha mRNA and protein also lacked HSP27 immunoreactivity. ERalpha gene expression at the mRNA level significantly correlated with the immunoprofile of the estrogen-inducible HSP27 protein in androgen-insensitive prostatic adenocarcinomas. This may indicate that these tumors harbor functional active estrogen receptors promoting transcriptional activity of the HSP27 gene. Determination of the receptor status by immunohistochemistry is unable to identify neoplastic lesions with established ERalpha mRNA expression in a substantial number of cases. HSP27 may be an additional surrogate biomarker for estrogen-regulated growth in androgen-insensitive prostate cancer.