Abstract 536: Insulin-like growth factor II (IGF-II) is a potential target for the treatment of triple negative breast cancers (TNBC).

Abstract 536: Insulin-like growth factor II(IGF-II) is a potential target for the treatment oftriple negative breast cancers (TNBC). Vinodh Kumar Radhakrishnan, Qianwei Tan, Marino A. De Leon, andDaisy D. De Leon Author AffiliationsProceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC Abstract In the United States, African American (AA) women have a lower incidence of breastcancer compared to Caucasian (CA) women, but higher overall mortality. Our lab havedemonstrated that Breast Cancer from AA patients express significantly higher levels ofIGF-II and show a higher activation of the IGF signaling system in African American (AA)when compared to Caucasian (CA) women. We showed that IGF-II promotes breast cancerprogression and metastasis by inhibiting tumor cell death and promoting resistance tochemotherapy, thus contributing to increased breast cancer (BC) mortality. This study wasdesigned to determine how IGF-II contributes to the aggressiveness of TNBC, the mostdeadly of breast tumors, which is highly prevalent among AA. To analyze IGF-II in a TNBCcell model, we chose cell lines established from tumors of AA and CA breast cancerpatients. Expression of IGF-II and IGF-II regulated proteins mRNA expression was probedusing the CFX96 real time PCR system. Similarly, IGF-II and related proteins expressionwas analyzed by western blots and chemiluminescence. We also characterized theepigenetic activation of IGF-II in these cell lines since variation in the expression of IGF-IIalleles regulates a signature of proteins associated with tumor aggressiveness. Our excitingresults demonstrated that higher IGF-II levels in TNBC cells from AA was associated withdistinct epigenetic changes that included different promoter activation and higher levels ofIGF-II translation which are inheritable traits. In contrast, TNBC from CA had higher IGF-IIlevels due to different molecular IGF-II regulation. Thus, IGF-II is an important biomarkerand can be used as therapeutic target for treatment of TNBC.