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

• Published in: Cancer research (Chicago, Ill.) Vol. 73; no. 8_Supplement; p. 536
• Main Authors: Radhakrishnan, Vinodh Kumar, Tan, Qianwei, De León, Marino A., De León, Daisy D.
• Format: Journal Article
• Language: English
• Published: 15.04.2013
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/1538-7445.AM2013-536

Abstract In the United States, African American (AA) women have a lower incidence of breast cancer compared to Caucasian (CA) women, but higher overall mortality. Our lab have demonstrated that Breast Cancer from AA patients express significantly higher levels of IGF-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 cancer progression and metastasis by inhibiting tumor cell death and promoting resistance to chemotherapy, thus contributing to increased breast cancer (BC) mortality. This study was designed to determine how IGF-II contributes to the aggressiveness of TNBC, the most deadly of breast tumors, which is highly prevalent among AA. To analyze IGF-II in a TNBC cell model, we chose cell lines established from tumors of AA and CA breast cancer patients. Expression of IGF-II and IGF-II regulated proteins mRNA expression was probed using the CFX96 real time PCR system. Similarly, IGF-II and related proteins expression was analyzed by western blots and chemiluminescence. We also characterized the epigenetic activation of IGF-II in these cell lines since variation in the expression of IGF-II alleles regulates a signature of proteins associated with tumor aggressiveness. Our exciting results demonstrated that higher IGF-II levels in TNBC cells from AA was associated with distinct epigenetic changes that included different promoter activation and higher levels of IGF-II translation which are inheritable traits. In contrast, TNBC from CA had higher IGF-II levels due to different molecular IGF-II regulation. Thus, IGF-II is an important biomarker and can be used as therapeutic target for treatment of TNBC. Citation Format: Vinodh Kumar Radhakrishnan, Qianwei Tan, Marino A. De León, Daisy D. De León. Insulin-like growth factor II (IGF-II) is a potential target for the treatment of triple negative breast cancers (TNBC). [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 536. doi:10.1158/1538-7445.AM2013-536