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Castration‐induced epithelial cell death in human prostate tissue is related to locally reduced IGF‐1 levels
Author(s) -
Ohlson Nina,
Bergh Anders,
Stattin Pär,
Wikström Pernilla
Publication year - 2006
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20480
Subject(s) - stroma , prostate , epithelium , castration , prostate cancer , medicine , endocrinology , apoptosis , biology , androgen receptor , andrology , immunohistochemistry , pathology , cancer , hormone , biochemistry
Abstract BACKGROUND Castration rapidly reduces stroma insulin‐like growth factor (IGF)‐1 synthesis and action in mouse prostate epithelium. We explore if similar changes are of importance for castration‐induced prostate regression in humans. METHODS Epithelial and surrounding stroma cells were micro‐dissected from patient biopsies obtained before and shortly after castration. IGF‐1 mRNA levels were quantified by RT‐PCR and related to epithelial apoptosis and IGF‐1, IGF‐1 receptor, and androgen receptor (AR) immunoreactivity. RESULTS IGF‐1 mRNA was principally produced in the stroma and IGF‐R1 in the epithelium. Stroma IGF‐1 mRNA levels were significantly decreased after castration in non‐malignant but not malignant tissue. Lack of stroma IGF‐1 reduction after castration was associated with low stroma AR expression before therapy. Reduction of IGF‐1 mRNA levels in the tumor stroma and/or epithelium was associated with epithelial apoptosis after therapy. CONCLUSIONS Low AR expression and maintained stroma IGF‐1 synthesis may result in limited tumor cell death after castration therapy. Prostate 67:32–40, 2007. © 2006 Wiley‐Liss, Inc.