Abstract 1127: Dysregulation of tumor suppress gene LKB1 in pancreatic cancer

Abstract

Abstract Pancreatic cancer is the fourth leading causes of cancer-related death in USA and the most common seen neoplsams in Peutz-Jeghers syndrome (PJS). PJS is an autosomal dominant disorder characterized by gastrointestinal hamartoma and predisposition to cancer. Patients with PJS have a 100-fold higher risk for development of pancreatic cancer than the general population. Tumor suppressor LKB1 is the causative gene for PJS. LKB1 mutations have also been observed in a significant proportion of sporadic pancreatic cancer, suggesting a role for LKB1 in pancreatic cancer although the underlying mechanism has not been elucidated yet. To evaluate the role of LKB1 in pancreatic tumorigenesis, we extracted RNA from our unique collection of fifty-three tumor/normal pairs of snap frozen pancreatic cancer and adjacent normal tissue from the same patient. RT-PCR results showed that LKB1 is downregulated in ∼74% of the cancer tissue compared to adjacent normal pair, and in ∼40% of pairs the downregaulation is greater than 2 folds. To confirm our result, we analyzed the publically available gene expression microarray data on 36 pancreatic cancer samples and 12 normal controls. We observed downregulation of LKB1 in these data and the difference in LKB1 expression levels in pancreatic cancer vs normal was statistically significant (p=0.0003). LKB1 has been reported to negatively regulate mTOR signaling. Therefore, we further analyzed whether there was correlation between the expression of LKB1 and key protein in mTOR signaling pathway. Our results showed that the expression of LKB1 is inversely correlated with that of EIF4A and EIF4E, which are translation initiation factors. These findings suggest that dysregulation of LKB1 and its downstream signaling pathway may play an important role in pancreatic 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 1127.