Abstract 538: IGF2 role in trastuzumab-resistance in JIMT-1 cells.

Abstract Breast cancer is the second leading cause of death in women. Overexpression of Human Epidermal Growth Factor Receptor 2 (HER2) is detected in 20-30% of breast cancers. Overexpression of HER2 is linked to poor prognosis, more aggressive phenotype, and resistance to chemotherapy and hormonal treatment. HER2 is part of a four member family of cell surface receptors that are implicated in transmission of signals controlling cell growth and differentiation. HER2 has an intracellular domain with tyrosine kinase catalytic activity. Dimerization of HER2 activates the MAP kinase and AKT pathways. HER2 receptor also heterodimerizes with the IGF1 receptor in trastuzumab-resistant cell lines. The insulin-like growth factor 2 (IGF2) has an important role in fetal and cancer development signaling through the insulin-like growth factor 1 receptor (IGF1R), the insulin receptor (InsR), and cross-talk with the estrogen receptor alpha and beta (ERα, ERß). We hypothesize that IGF2 mediates trastuzumab-resistance in JIMT-1 cell line. IGF2 mRNA and protein levels were determined in trastuzumab-sensitive cell lines (BT474, SKBR3, and ZR 75-30) and trastuzumab-resistant cell line (JIMT-1) by qPCR and Western blot. We also analyzed the effect of IGF2 inhibition treatment on the phosphorylation levels of HER2. Our study showed that IGF2 increases in trastuzumab-resistant cell line, JIMT-1. Furthermore, inhibition of IGF2 decreases JIMT-1 cell viability compared to control and renders cells sensitive to trastuzumab. These findings provide a potential therapy target for trastuzumab-resistant breast cancers. Citation Format: Xousaen M. Helu, Daisy D. De Leon. IGF2 role in trastuzumab-resistance in JIMT-1 cells. [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 538. doi:10.1158/1538-7445.AM2013-538