Abstract 533: Differential expression of IGF-II in Vietnamese women in triple negative breast cancer is dependent on biallelic or monoallelic IGF-II with ApaI SNP.

Triple negative breast cancer (TNBC) is more likely to be advanced, poorly differentiated, larger, and present in women of younger age and of lower socioeconomic status. Moreover, TNBC patients have worse outcomes when treated with currently available adjuvant chemotherapy. We have demonstrated that Breast cancer (BC) tumors from AA patients express significantly higher levels of IGF-II compared to Caucasian women (CA), and show a higher activation of the IGF signaling pathways in tumors progression (Kalla et.al., 2010). Thus we designed a study in younger Vietnamese women where TNBC incidence is increasing. A total of 24 paired BC samples were analyzed by gDNA PCR for IGF-II Apa I polymorphism to correlate with IGF-II mRNA and protein levels. The levels of IGF-II correlated with the imprinting status, i.e., Biallelic (BA; n=14)>>, Monoallelic with SNP (MAS; n=5)>, and Monoallelic non-ApaI SNP (MA; n=5)>. Higher IGF-II levels were expressed in tumor as compared to normal BC tissue samples. The free proIGF-II protein and mRNA levels were higher in biallelic tumor tissues as compared to the proIGF-II levels detected in monoallelic tumor samples. The growth factor receptors; Insulin receptor A (IRA), Insulin receptor B (IRB), Vascular endothelial growth factor receptor (VEGFR), Estrogen receptor-1 (ESR1), Progesterone receptor (PGR) and Human epidermal growth factor receptor (ERBB2) levels were determined to show if IGF-II monoallelic or biallelic dosage regulated the receptor levels. We conclude that biallelic IGF-II expression in TNBC tumors results in higher IGF-II mRNA, protein and related receptors levels than in monoallelic samples. Citation Format: Vinodh Kumar Radhakrishnan, Qianwei Tan, Marino A. De Leon, Daisy D. De Leon. Differential expression of IGF-II in Vietnamese women in triple negative breast cancer is dependent on biallelic or monoallelic IGF-II with ApaI SNP. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 533. doi:10.1158/1538-7445.AM2013-533