Insulin receptor expression by human prostate cancers.
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.


CONCLUSIONS
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.
Cox
Michael E
ME
The Prostate Center at Vancouver General Hospital, University of British Columbia, Vancouver, British Columbia, Canada.
Gleave
Martin E
ME
Zakikhani
Mahvash
M
Bell
Robert H
RH
Piura
Esther
E
Vickers
Elaine
E
Cunningham
Matthew
M
Larsson
Ola
O
Fazli
Ladan
L
Pollak
Michael
M
D000918:Antibody Specificity; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D006946:Hyperinsulinism / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D007150:Immunohistochemistry; D008113:Liver Neoplasms; D008297:Male; D024821:Metabolic Syndrome / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology; D009765:Obesity / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D020411:Oligonucleotide Array Sequence Analysis; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000276:immunology / Q000378:metabolism; D011972:Receptor, Insulin / Q000235:genetics* / Q000276:immunology / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology
D012333:RNA, Messenger; D017526:Receptor, IGF Type 1; D011972:Receptor, Insulin