Abstract 3925: IGF2 activation of HER2 receptor in HER2 positive breast cancer cell lines

Abstract

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 and dimerization of HER2 activates the MAP kinase and AKT pathways. HER2 receptor also heterodimerizes with the IGF1 receptor and can be activated by IGF1 receptor ligand. 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), insulin receptor (InsR), and cross-talk with the estrogen receptor alpha and beta (ERα, ERß). We hypothesized that binding of IGF-II to the IGF-1R/HER2 dimer may activate the HER2 signaling pathway. We characterized the IGF2 mRNA and protein levels in HER2 positive cell lines (BT474, SKBR3, and ZR 75-30) by qPCR and Western blot. We also analyzed the effect of IGF2 treatment on the phosphorylation levels of HER2. We measured the signaling levels of HER2 and IGF1R in the presence and absence of IGF2. Our study showed that IGF2 increases HER2 phosphorylation. Furthermore, blocking IGF1R increases HER2 protein levels. Thus, we propose that IGF2 has an important role in the activation of HER2 signaling pathway. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 3925. doi:1538-7445.AM2012-3925