Abstract 996: Receptor tyrosine kinase AXL is upregulated in metformin resistant prostate cancer cells.

Abstract

Abstract Metformin is a biguanine derivative, widely used as an antidiabetic drug. Epidemiological studies on several types of cancers including breast, prostate, ovarian and pancreatic cancer show that patients treated with metformin have a lower incidence of cancer. Mechanistic studies have shown that metformin inhibits cancer cell viability by activating the AMP activated protein kinase (AMPK) pathway and inhibiting mTOR. In this study we developed a metformin resistance LnCap prostate cancer cells by exposing the cells continuously increasing concentrations of metformin. Micro-array data analysis comparing the resistant cells (4-fold) to parental cells showed that genes associated with receptor binding and with cell proliferation are primarily affected. EDIL3 (EGF-like repeats and discoidin I-like domains 3), EREG (eEpiregulin) and AXL (Axl receptor tyrosine kinase) are top three up regulated genes (∼ 35 fold). CALB2 (cCalbindin 2) and TPTE (transmembrane phosphatase with tensin homology) were the top down regulated genes (10 fold down regulated). AXL overexpression has earlier been demonstrated in Imatinib resistant CML cell lines and in CML cells from patients. We are currently investigating the role of Axl receptor tyrosine kinase in metformin resistant prostate cancer cells. Citation Format: Nitu Bansal, Prasun Mishra, Kathleen Cruz, Joseph Bertino. Receptor tyrosine kinase AXL is upregulated in metformin resistant prostate cancer 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 996. doi:10.1158/1538-7445.AM2013-996