Insulin receptor expression by human prostate cancers

Abstract

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.

Expression of the IGF Axis Is Decreased in Local Prostate Cancer but Enhanced after Benign Prostate Epithelial Differentiation and TGF-β Treatment

“…In addition, the results from these analyses often failed to be consistent. IGF1R levels were reported to be down-regulated, 14 up-regulated, 15,16 or not changed 17,18 in local prostate cancer. The IGF1R is a tyrosine kinase receptor.…”

“…The results reported were often inconsistent. For example, IGF1R levels were reported to be down-regulated, 14 up-regulated, 15,16 or not changed 17,18 in local prostate cancer. Clinical trials investigating the therapeutic efficacy of an anti-IGF1R therapy in prostate cancer are registered in the US National Institutes of Health database of clinical studies (http://www.clinicaltrials.gov).…”

Obese men have higher-grade and larger tumors: an analysis of the duke prostate center database

“…In general, obese men have higher insulin levels than normal weight men, 16 and prostate cancers have recently been shown to express the insulin receptor at high levels. 17 Moreover, in multiple studies higher insulin levels among men with prostate cancer have been linked with prostate cancer death. 18,19 In addition, obese men have lower androgen levels, which may promote more aggressive cancers, 20 though this remains a controversial hypothesis.…”

Insulinlike Growth Factor-1Ec (MGF) Expression in Eutopic and Ectopic Endometrium: Characterization of the MGF E-Peptide Actions In Vitro

“…The latter is composed of an IR hemi-receptor linked to an IGF-IR hemi-receptor and has been reported to have an important role in cancer biology (29)(30)(31). Recently, the two IR isoforms (IR-A and IR-B) have been reported that are overexpressed in cancer tissues (32), whereas the expression of IGF-1R has been previously characterized in KLE cells in our laboratory (7). Therefore, aiming to the characterize the MGF E-peptide actions in KLE cells, we performed a series of silencing experiments of these major receptors involved in the IGFmediated actions.…”