Abstract 1277: Utilizing uterine cancer models to study malignant transformation driven by Lkb1 loss.

Abstract

Abstract The serine-threonine kinase LKB1 is an upstream component of the AMPK-mTOR pathway and regulates cell survival and growth. Inherited germline mutations in LKB1 predispose women to endocervical malignancies whereas somatic mutations in LKB1 promote cervical cancer progression. Our lab has shown that tissue specific knockout of Lkb1 in the endometrial epithelium of mice facilitates growth of highly invasive, lethal tumors that are well differentiated and retain structural polarity. Additionally, stable shRNA mediated knockdown of LKB1 in human immortalized endocervical cells drives anchorage-independent growth. To investigate potential pathways involved in LKB1 mediated oncogenic transformation, we have employed a microarray based approach comparing hits from human immortalized endocervical cell lines and mouse tissue to identify specific genes that are differentially regulated when LKB1 function is absent. Preliminary data suggests that pro-angiogenic and inflammatory mediators are upregulated in LKB1 deficient cells. We are currently assessing the overall contribution of these factors to growth and invasiveness in our model systems and the mechanisms by which Lkb1 loss facilitates their activation. These pathways can be potential therapeutic targets in other cancers characterized by Lkb1 loss of function mutations. Citation Format: Christopher G. Peña, Yuji Nakada, Diego Castrillon. Utilizing uterine cancer models to study malignant transformation driven by Lkb1 loss. [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 1277. doi:10.1158/1538-7445.AM2013-1277