Premium
Insulin receptor expression by human prostate cancers
Author(s) -
Cox Michael E.,
Gleave Martin E.,
Zakikhani Mahvash,
Bell Robert H.,
Piura Esther,
Vickers Elaine,
Cunningham Matthew,
Larsson Ola,
Fazli Ladan,
Pollak Michael
Publication year - 2008
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.20852
Subject(s) - prostate cancer , hyperinsulinemia , prostate , insulin receptor , receptor , medicine , endocrinology , insulin , cancer , tissue microarray , cancer research , biology , insulin resistance
BACKGROUND Although recent laboratory and population studies suggest that prostate cancer may be responsive to insulin, there is a gap in knowledge concerning the expression of insulin receptors on benign or malignant prostate tissue. METHODS We immunostained 644 cores on tissue microarrays prepared from 29 prostate tissue samples without malignancies, 78 Gleason grade 3 cancers, 21 Gleason grade 4 cancers and 33 Gleason grade 5 cancers with antibodies against the insulin‐like growth factor I receptor and the insulin receptor. RESULTS We observed immunoreactivity with both antibodies, which implies the presence of hybrid receptors as well as IGF‐I receptors and insulin receptors. Insulin receptor staining intensity was significantly ( P < 0.001) higher on malignant than benign prostate epithelial cells. Analysis of information from public gene expression databases confirmed that co‐expression of insulin receptor mRNA and IGF‐I receptor mRNA is common in prostate cancer specimens. RT‐PCR methods provided evidence for the presence of mRNA for both IR‐A and IR‐B insulin receptor isoforms. CONCLUSION These observations document the presence of insulin receptors on primary human prostate cancers. The findings are relevant not only to ongoing clinical trials of drug candidates that target IGF‐I and/or insulin receptors, but also to the hypothesis that obesity‐associated hyperinsulinemia mediates the adverse effect of obesity on prostate cancer prognosis. Prostate 69: 33–40, 2009. © 2008 Wiley–Liss, Inc.