@article {1634922,
	title = {Expression of IGF/insulin receptor in prostate cancer tissue and progression to lethal disease},
	journal = {Carcinogenesis},
	volume = {39},
	number = {12},
	year = {2018},
	month = {2018 Dec 31},
	pages = {1431-1437},
	abstract = {Circulating insulin-like growth factor-1 (IGF-1) is consistently associated with prostate cancer risk. IGF-1 binds to IGF-1 receptor (IGF1R) and insulin receptor (IR), activating cancer hallmark pathways. Experimental evidence suggests that TMPRSS2:ERG may interact with IGF/insulin signaling to influence progression. We investigated IGF1R and IR expression and its association with lethal prostate cancer among 769 men. Protein expression of IGF1R, IR and ERG (i.e. a surrogate of ERG fusion genes) were assayed by immunohistochemistry. Cox models estimated hazard ratios (HR) and 95\% confidence intervals (CI) adjusted for clinical characteristics. Among patients, 29\% had strong tumor IGF1R expression and 10\% had strong IR expression. During a mean follow-up of 13.2 years through 2012, 80 men (11\%) developed lethal disease. Tumors with strong IGF1R or IR expression showed increased cell proliferation, decreased apoptosis and a higher prevalence of ERG. In multivariable models, strong IGF1R was associated with a borderline increased risk of lethal prostate cancer (HR 1.7; 95\% CI 0.9-3.1). The association appeared greater in ERG-positive tumors (HR 2.8; 95\% CI 0.9-8.4) than in ERG-negative tumors (HR 1.3; 95\% CI 0.6-3.0, p-heterogeneity 0.08). There was no association between IR and lethal prostate cancer (HR 0.8; 95\% CI 0.4-1.9). These results suggest that tumor IGF1R expression may play a role in prostate cancer progression to a lethal phenotype and that ERG-positive tumors may be more sensitive to IGF signaling. These data may improve our understanding of IGF signaling in prostate cancer and suggest therapeutic options for disease subtypes.},
	keywords = {Aged, Apoptosis, Biomarkers, Tumor, Cell Proliferation, Disease Progression, Gene Expression Regulation, Neoplastic, Humans, Insulin, Insulin-Like Growth Factor I, Male, Oncogene Proteins, Fusion, Prostatic Neoplasms, Receptor, IGF Type 1, Receptor, Insulin, Receptors, Somatomedin, Signal Transduction, Transcriptional Regulator ERG},
	issn = {1460-2180},
	doi = {10.1093/carcin/bgy112},
	author = {Ahearn, Thomas U and Peisch, Sam and Pettersson, Andreas and Ebot, Ericka M and Zhou, Cindy Ke and Graff, Rebecca E and Sinnott, Jennifer A and Fazli, Ladan and Judson, Gregory L and Bismar, Tarek A and Rider, Jennifer R and Gerke, Travis and Chan, June M and Fiorentino, Michelangelo and Flavin, Richard and Sesso, Howard D and Finn, Stephen and Giovannucci, Edward L and Gleave, Martin and Loda, Massimo and Li, Zhe and Pollak, Michael and Mucci, Lorelei A}
}
