Insulin Receptor Expression by Human Prostate Cancers
Insulin Receptor Expression by Human Prostate Cancers
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DOI：
10.1002/pros.20852
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发表时间：
2009-01-01
期刊：
影响因子：
2.8
通讯作者：
Pollak, Michael
中科院分区：
文献类型：
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作者：
Cox, Michael E.;Gleave, Martin E.;Pollak, Michael
背景尽管最近的实验室和人群研究表明前列腺癌可能对胰岛素有反应，但关于良性或恶性前列腺组织上胰岛素受体表达的知识存在空白。我们用抗胰岛素样生长因子I受体和胰岛素受体的抗体对29例无恶性肿瘤的前列腺组织样本、78例Gleason 3级癌症、21例Gleason 4级癌症和33例Gleason 5级癌症的组织微阵列上的644个核心进行免疫染色。我们观察到两种抗体的免疫反应性，这意味着存在杂交受体以及IGF-I受体和胰岛素受体。恶性前列腺上皮细胞胰岛素受体染色强度显著高于良性前列腺上皮细胞（P < 0.001）。对公共基因表达数据库的信息分析证实，胰岛素受体mRNA和IGF-I受体mRNA的共表达在前列腺癌标本中很常见。RT-PCR方法证实了IR-A和IR-B胰岛素受体亚型mRNA的存在。这些观察结果证明了胰岛素受体在原发性人前列腺癌中的存在。这些发现不仅与正在进行的靶向IGF-I和/或胰岛素受体的候选药物的临床试验有关，而且与肥胖相关的高胰岛素血症介导肥胖对前列腺癌预后的不利影响的假设有关。前列腺69：33- 40，2009。(C)2008威利利斯公司
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 epithelia 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 I R-A and IR-B insulin receptor isoforms.CONCLUSION. These observations document the presence Of insulin receptors oil 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 ad verse effect of obesity on prostate cancer prognosis. Prostate 69:33-40,2009. (C) 2008 Wiley-Liss, Inc.