Abstract 3131: Higher IGF-II expression in Vietnamese triple negative breast cancer tumors 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. In the United States, African American (AA) women have a lower incidence of breast cancer compared with Caucasian women (CA), but higher overall mortality. Our lab have demonstrated that BC tumors from AA patients express significantly higher levels of IGF-II and show a higher activation of the IGF signaling pathways (Kalla et.al., 2010a, 2010b). IGF-II levels regulate survival proteins and activate the ER signaling pathway promoting an aggressive tumor development. Thus we designed a study to determine if IGF-II regulates the progression of TNBC tumors. TNBC incidence is increasing in younger Vietnamese women. Thus, we designed a study to analyze the IGF-II expression in paired normal-tumor BC tissues from Vietnamese TNBC patients. Furthermore, we decided to characterize the IGF-II genomic imprinting status, to correlate IGF-II levels with Monoallelic or Biallelic IGF-II gene expression. A total of 24 paired BC samples obtained from ILSbio were analyzed by Western Blot, RT-PCR and gDNA PCR with Apa I restriction digestion. Our results showed that the IGF-II genomic imprinting status in all 24 pairs was the same in normal and tumor tissues from the same patient. 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 tissue from the same patient. The free proIGF-II protein levels were 6.5-15.22 fold higher in biallelic tumor tissues as compared to the proIGF-II levels detected in monoallelic tumor samples. The IGF-II mRNA levels were 0.4-1 fold higher in biallelic tumor tissues as compared to the proIGF-II levels detected in monoallelic tumor samples. We also assessed 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) status to determine 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 and protein levels than in monoalle