Expression of IGF/insulin receptor in prostate cancer tissue and progression to lethal disease.

Publisher: Irl Press At Oxford University Press Country of Publication: England NLM ID: 8008055 Publication Model: Print Cited Medium: Internet ISSN: 1460-2180 (Electronic) Linking ISSN: 01433334 NLM ISO Abbreviation: Carcinogenesis Subsets: MEDLINE

Publication: Oxford : Irl Press At Oxford University Press
Original Publication: [New York, IRL Press]

Insulin-Like Growth Factor I/*genetics ; Prostatic Neoplasms/*genetics ; Prostatic Neoplasms/*pathology ; Receptor, Insulin/*genetics ; Receptors, Somatomedin/*genetics; Aged ; Apoptosis/genetics ; Biomarkers, Tumor/genetics ; Cell Proliferation/genetics ; Disease Progression ; Gene Expression Regulation, Neoplastic/genetics ; Humans ; Insulin/genetics ; Male ; Oncogene Proteins, Fusion/genetics ; Receptor, IGF Type 1 ; Signal Transduction/genetics ; Transcriptional Regulator ERG/genetics

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.

Prostate. 2011 Apr;71(5):489-97. (PMID: 20878952)
Cancer Res. 2016 Apr 15;76(8):2288-2300. (PMID: 26921328)
Eur Urol. 2009 Aug;56(2):275-86. (PMID: 19409690)
Mol Endocrinol. 2015 Dec;29(12):1694-707. (PMID: 26452103)
J Natl Cancer Inst. 2014 Jun;106(6):dju085. (PMID: 24824313)
BMC Cancer. 2017 May 25;17(1):367. (PMID: 28545426)
Int J Cancer. 2009 May 15;124(10):2416-29. (PMID: 19142965)
Curr Opin Pharmacol. 2008 Aug;8(4):384-92. (PMID: 18674638)
J Cell Biochem. 2006 Oct 1;99(2):392-401. (PMID: 16639715)
J Pathol. 2009 Mar;217(4):469-82. (PMID: 19148905)
Prostate. 2009 Jan 1;69(1):33-40. (PMID: 18785179)
Int J Cancer. 2007 Jun 15;120(12):2678-86. (PMID: 17278097)
Oncotarget. 2014 May 15;5(9):2723-35. (PMID: 24809298)
Cancer Epidemiol Biomarkers Prev. 2013 Nov;22(11):1984-93. (PMID: 23983239)
Endocrinology. 2012 Oct;153(10):4633-43. (PMID: 22903612)
Prev Med. 1985 Mar;14(2):165-8. (PMID: 3900975)
Int J Cancer. 2015 May 15;136(10):2418-26. (PMID: 25348852)
Cancer Epidemiol Biomarkers Prev. 2012 Sep;21(9):1497-509. (PMID: 22736790)
Cancer Causes Control. 2012 Feb;23(2):347-54. (PMID: 22183619)
Nat Rev Cancer. 2008 Dec;8(12):915-28. (PMID: 19029956)
Cancer Causes Control. 2014 May;25(5):625-32. (PMID: 24664287)
Int J Cancer. 2007 Oct 1;121(7):1571-8. (PMID: 17450530)
JAMA. 2009 Jan 7;301(1):52-62. (PMID: 19066368)
Endocr Rev. 2009 Oct;30(6):586-623. (PMID: 19752219)
Int J Cancer. 2011 Feb 1;128(3):660-7. (PMID: 20473871)
Cancer Prev Res (Phila). 2010 Oct;3(10):1334-41. (PMID: 20858760)
Cancer Epidemiol Biomarkers Prev. 2007 Jun;16(6):1121-7. (PMID: 17548673)
J Natl Cancer Inst. 2002 Jul 17;94(14):1099-106. (PMID: 12122101)
J Clin Oncol. 2009 Jul 20;27(21):3459-64. (PMID: 19433685)
Endocr Relat Cancer. 2013 Mar 22;20(2):173-86. (PMID: 23319492)
Oncotarget. 2016 Aug 9;7(32):51375-51392. (PMID: 27285981)
J Cell Physiol. 2012 Feb;227(2):751-8. (PMID: 21465482)
J Natl Cancer Inst. 2015 Nov 27;108(2):. (PMID: 26615022)
Oncotarget. 2015 Jun 30;6(18):16611-22. (PMID: 25906745)
Mol Cancer Ther. 2014 Dec;13(12):2827-39. (PMID: 25267499)
Cancer Epidemiol Biomarkers Prev. 2012 Sep;21(9):1531-41. (PMID: 22761305)
Nat Rev Cancer. 2004 Jul;4(7):505-18. (PMID: 15229476)
Lancet Oncol. 2008 Nov;9(11):1039-47. (PMID: 18835745)
Ann Intern Med. 2008 Oct 7;149(7):461-71, W83-8. (PMID: 18838726)
Cancer Prev Res (Phila). 2010 Mar;3(3):279-89. (PMID: 20179296)
Cell. 2015 Nov 5;163(4):1011-25. (PMID: 26544944)
J Clin Oncol. 2009 Nov 20;27(33):5627-33. (PMID: 19858401)
J Natl Cancer Inst. 2013 Dec 18;105(24):1881-90. (PMID: 24292212)
Cancer Res. 2008 Aug 1;68(15):6260-70. (PMID: 18676850)
Mol Cancer Ther. 2013 Apr;12(4):394-404. (PMID: 23348048)

P50 CA090381 United States CA NCI NIH HHS; U01 CA167552 United States CA NCI NIH HHS; R01 CA141298 United States CA NCI NIH HHS; R25 CA112355 United States CA NCI NIH HHS; UM1 CA167552 United States CA NCI NIH HHS; R01 CA136578 United States CA NCI NIH HHS; P30 CA006516 United States CA NCI NIH HHS

0 (Biomarkers, Tumor)
0 (IGF1 protein, human)
0 (IGF1R protein, human)
0 (Insulin)
0 (Oncogene Proteins, Fusion)
0 (Receptors, Somatomedin)
0 (Transcriptional Regulator ERG)
67763-96-6 (Insulin-Like Growth Factor I)
EC 2.7.10.1 (Receptor, IGF Type 1)
EC 2.7.10.1 (Receptor, Insulin)

Date Created: 20180831 Date Completed: 20190613 Latest Revision: 20240408

20250114

PMC6314328

10.1093/carcin/bgy112

30165429