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

Abstract

BACKGROUND The recent discovery of the classical estrogen receptor α (ERα) 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 ERα gene expression, and the estrogen‐inducible heat shock protein HSP27 in recurrent prostatic adenocarcinomas. METHODS Palliative transurethral resection specimens from 50 patients with androgen‐insensitive disease were submitted for study. Messenger RNA in situ hybridization for the ERα and immunohistochemistry of the HSP27 protein were performed on adjacent sections of an equal number of prostate cancer tissue with and without ERα protein expression. RESULTS Cancerous lesions lacking the nuclear ERα at the protein level revealed ERα mRNA expression in 15 of 25 cases (60%). A coordinate expression of ERα mRNA and HSP27 was observed in 33 of 40 cases (83%), although a significant correlation between ERα protein and HSP27 expression was not obtained. Conversely, 90% of neoplastic lesions without detectable levels of ERα mRNA and protein also lacked HSP27 immunoreactivity. CONCLUSIONS ERα 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 ERα mRNA expression in a substantial number of cases. HSP27 may be an additional surrogate biomarker for estrogen‐regulated growth in androgen‐insensitive prostate cancer. Prostate 45:36–41, 2000. © 2000 Wiley‐Liss, Inc.

Hsp27 knockdown using nucleotide-based therapies inhibit tumor growth and enhance chemotherapy in human bladder cancer cells

“…Hsp27 expression is increased in a variety of malignancies, including prostate (6), breast (7), gastric (8), ovarian (9), and bladder cancers (10,11). Furthermore, Hsp27 overexpression has been associated with multidrug resistance (12) and direct inhibition of apoptosis (13,14) and is functionally linked to increased tumorigenicity and treatment resistance in breast (15) and colon (16) cancers.…”

Heat Shock Protein 27 Increases after Androgen Ablation and Plays a Cytoprotective Role in Hormone-Refractory Prostate Cancer

“…Hsp27 belongs to a family of chaperone proteins that modulate a diverse range of cytoprotective, homeostatic, and pathogenic intracellular activities (13)(14)(15)(16)(17). In neoplasia, Hsps are associated with multidrug resistance (18) and apoptosis (19,20) and are functionally linked to increased tumorigenicity and treatment resistance in breast (21)(22)(23)(24) and colon (25,26) cancers.…”

2‐methoxyestradiol blocks cell‐cycle progression at G2/M phase and inhibits growth of human prostate cancer cells

“…Moreover, short‐term simultaneous treatment (16 wk) of Noble rats with testosterone and estradiol induced intraductal dysplasia in the dorsolateral lobe of the prostate gland, but prolonged treatment (52 wk) resulted in a high incidence of prostatic carcinoma [9]. Various forms of estrogen receptors (ERs) also have been found in prostate cancer cell lines and prostate tumors, including a novel form of ER‐β that is expressed in the epithelial compartment of the prostate [10–13].…”

“…It has been shown that a vast majority of prostate adenocarcinomas that recur after androgen‐deprivation therapy express the classic ER‐α at the protein and mRNA levels [10]. Furthermore, ER ‐β knockout mice exhibit prostatic hyperplasia [14].…”