Castration-induced epithelial cell death in human prostate tissue is related to locally reduced IGF-1 levels.
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.
Ohlson
Nina
N
Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
Bergh
Anders
A
Stattin
Pär
P
Wikström
Pernilla
P
D017209:Apoptosis / Q000235:genetics / Q000502:physiology; D016923:Cell Death / Q000235:genetics / Q000502:physiology; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology / Q000502:physiology*; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D009919:Orchiectomy; D011467:Prostate / Q000378:metabolism* / Q000473:pathology / Q000601:surgery; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D017154:Stromal Cells / Q000378:metabolism / Q000473:pathology
D012333:RNA, Messenger; D007334:Insulin-Like Growth Factor I