Abstract C66: Insulin-like growth factor binding protein-6 is differentially methylated in African American, African, and Amish HapMap cell lines

Abstract

Abstract African American women, while having lower lifetime incidence of breast cancer (BrCa) than Caucasian women, have higher BrCa mortality rates, partially due to a higher incidence of the more aggressive, basal-like molecular subtype of BrCa. Correlations of this subtype within African ancestral groups suggest a potential link to African Ancestry and basal-like BrCa. While socioeconomic factors may also play a role in higher mortality rates, there is mounting evidence that the differential epigenetic regulation of cancer genes may also contribute to this disparity. To address this, our lab is investigating the epigenetic regulation of genes in the insulin-like growth factor pathway using qPCR, Immunohistochemistry (IHC) and Bisulfite-DNA Sequencing. This presentation specifically highlights novel data on the expression of insulin-like growth factor binding protein-6 (IGFBP-6), an IGF-II regulator and agent of cell proliferation, which has been shown previously to be epigenetically modified in cancer cells. Our qPCR and IHC data demonstrates higher IGFBP-6 transcription and protein expression in basal-like BrCa cells when compared to normal breast and ER+ BrCa cells. To address potential ancestry-specific expression, we also evaluated IGFBP-6 expression in African and African-American HapMap lymphoblast cell lines compared to CEPH-European (Amish) cell lines. Both qPCR and IHC data indicate higher overall expression of this gene in African lineages. Lastly, we have measured the differential methylation in two regions of the IGFBP-6 CpG island among African, African-American, and Amish cell lines. We show that IGFBP-6 methylation correlates with the expression patterns. Differential methylation could be due to Ancestral-Specific polymorphisms in this region, altering potential methylation sites. We conclude that the distinct levels of IGFBP-6 expression and promoter methylation in African and African-American cell lines may correspond to the increased incidence of basal-like BrCa in these populations, due to prolonged half-life and activity of the IGF-II growth signal. Our future studies include evaluation of whether this epigenetically-mediated up-regulation of IGFBP-6 directly leads to the excessive proliferation of basal-like tumors. Citation Format: DeJuana Ford, Briana Bennett, Myrielis Rivera, Rupali Hire, Melissa Davis. Insulin-like growth factor binding protein-6 is differentially methylated in African American, African, and Amish HapMap cell lines. [abstract]. In: Proceedings of the Sixth AACR Conference: The Science of Cancer Health Disparities; Dec 6–9, 2013; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2014;23(11 Suppl):Abstract nr C66. doi:10.1158/1538-7755.DISP13-C66