Abstract B25: Triple-negative breast tumors exhibit distinctive patterns of expression and subcellular localization of Insulin-like Growth Factor Binding Protein 6

Abstract

Abstract African-American women of all ages have higher breast cancer mortality rates than Caucasian women, despite lower breast cancer incidence among African-American women over 40. While differences in socioeconomic status and access to healthcare may play a role in this disparity, the disproportionately high occurrence of aggressive, triple-negative breast tumors in African-American women suggests a biological link between ancestry and breast cancer prognosis. Interestingly, both African ancestry and breast tumor aggressiveness are associated with distinct transcript and protein expression levels of Insulin-like growth factor-II (IGF-II) and its binding partner, Insulin-like growth factor binding protein 6 (IGFBP6), and we have previously observed higher levels of IGFBP6 transcript and protein expression in African-American and Yoruba (African) HapMap cell lines when compared to Amish cell lines. To gain a better understanding of potential mechanisms underlying these associations, we have investigated the expression and subcellular localization of these proteins and their transcripts using qPCR and immunofluorescence (IF). Our qPCR data indicate lower IGFBP6 transcript expression in breast cancer cells relative to normal cells, with lower transcript levels in the ER positive breast cancer cells than in triple negative cells. Conversely, our IF data revealed higher levels of IGFBP6 protein in ER positive breast cancer cells than in triple negative breast cancer cells, suggesting that breast tumor subtypes may be associated with unique patterns of transcript and protein regulation in these genes. We also observed a distinctive pattern of IGFBP6 subcellular localization in the triple-negative cells in which aggregates of this protein are localized at the edge of the nucleus, and co-localized with IGF-II. We hypothesize that IGF-II will be more dispersed throughout the nucleus following si-RNA knockdown of IGFBP6. Taken together, these data suggest the possibility of a subtype-specific IGF-II/IGFBP6 complex in triple negative breast cancer. Further studies will assess how this complex may promote tumor aggression in triple-negative breast tumors by inhibiting IGFBP6's IGF-independent, pro-apoptotic qualities within the nucleus and/or prolonging the half-life of IGF-II, thus promoting cancer cell growth. Citation Format: DeJuana Ford, Rupali Hire, Elizabeth Howerth, Briana Bennett, Krissean Lea, Jillian Hood, Melissa Davis. Triple-negative breast tumors exhibit distinctive patterns of expression and subcellular localization of Insulin-like Growth Factor Binding Protein 6. [abstract]. In: Proceedings of the Eighth AACR Conference on The Science of Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; Nov 13-16, 2015; Atlanta, GA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2016;25(3 Suppl):Abstract nr B25.