The omega-6 polyunsaturated fatty acid, linoleic acid (LA), is prevalent in Western diets and is known to enhance the tumorigenesis of mammary cancer models; with previous work demonstrating an upregulation of phosphatidylinositol-3-kinase (PI3K) signaling may play a key role. The Grb2-associated binding protein 1 (Gab1) is a scaffolding protein that can complex with the epidermal growth factor receptor (EGFR) to activate PI3K signaling. Recent studies in our laboratory reveal LA supplementation of the breast cancer cell lines MDA-MB-231 and BT-474 greatly increases the association between Gab1 and EGFR, while at the same time dramatically decreasing Gab1 protein levels. These changes are concomitant with increases in activated Akt (pAkt), a downstream signaling component in the PI3K signaling pathway. Moreover, inhibitors of EGFR and Gab1-specific siRNAs are capable of reversing LA-induced upregulation of pAkt, as well as observed increases in cell proliferation for these models. Finally, we were able to confirm these findings in the A549 lung cancer cell line, validating the potential relevance to tissues other than breast cancer cell lines. These data establish Gab1 as major target in LA-induced enhancement of tumorigenesis.

Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 5686.