Abstract 5344: IGF1-receptor expression is regulated by miR-100 in metastatic pancreatic cancer cells.

Abstract

Abstract Patients with pancreatic adenocarcinoma have the lowest 5-year survival and yearly rates of incidence are almost equivalent to the mortality rates. Long-term cure rates by standard therapies are disappointing due to disseminated disease at diagnosis and chemotherapeutic resistance. New therapeutic targets are necessary for decreasing the progression of pancreatic cancer and identifying targets specific to metastasis would improve patient care. In this study, we evaluated the levels of microRNA of metastatic and non-metastatic cell lines. The expression level of microRNAs and mRNAs were identified through microarray analysis by examining and comparing 5 pancreatic cancer cell lines, two that can metastasize in vivo (S2VP10, S2CP9) versus three that do not metastasize (MiaPaCa2, Panc-1, and ASPC-1). MicroRNA analysis indicated an increase in miR-100 and a decrease in miR-138 expression in metastatic cancer cells. Microarray analysis of differentially expressed mRNAs between metastatic and non-metastatic pancreatic cell lines also indicated increased insulin growth factor-1 receptor (IGF1-R) expression (p<0.0001) in metastatic pancreatic cancer cell lines compared to non-metastatic pancreatic cancer cell lines. To confirm these results from microarray analysis, western blot and immunocytochemistry was performed. Western blot revealed IGF1-R expression was 7 fold increased in metastatic cancer cell lines compared to non-metastastatic cell lines. In addition, downstream expressions of proteins GRB2 and phosphorylated PI3K also were increased in aggressive cancer cell lines. Immunocytochemistry confirmed the linkage of IGF1-R to miR-100 as cells transfected with miR-100 inhibitor showed a decrease in IGF1-R. However, cells transfected with a miR-138 mimic did not affect IGF1-R expression. IGF1-R may be an important molecular feature and a useful biomarker for diagnosis and treatment of metastatic pancreatic cancer. Citation Format: Justin S. Huang, Michael Egger, William E. Grizzle, Lacey R. McNally. IGF1-receptor expression is regulated by miR-100 in metastatic pancreatic 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 5344. doi:10.1158/1538-7445.AM2013-5344