Expression Of Recepteur D'origine Nantais(RON) In Pancreatic Cancer

Background & Objective: RON is a member of the c-MET receptor tyrosine kinase family, it resides in chromosome 3p21 region. RON is a 180 kDa heterodimeric protein composed of an extracellular 40kDaα-chain and a 145 kDa transmembraneβ-chain. The ligand for RON is the hepatocyte growth factor-like protein (HGFL) also known as macrophage-stimulating protein (MSP), RON activation mediates multiple signaling cascades including the c-Src, ras/mitogen-activated protein kinase (MAPK), phosphatidylinositol-3 kinase/Akt, and focal adhesion kinase pathways. RON activation in vitro induced cell transformation, growth, migration and matrix invasion. RON is expressed by a variety of epithelial-derived tumors and cancer cell lines such as human colorectal cancer, breast cancer and it is thought to play a functional role in tumorigenesis.The pathogenesis of pancreatic cancer is concealed, its progress is rapid, its prognosis is poor, and the mortality rate is high. Pancreatic cancer is the fourth leading cause of cancer-related mortality in the United States, accounting for >32,000 deaths in 2006, while it is the sixth leading cause of cancer-related mortality in China. Median survival for pancreatic cancer patients remains <1 year, and only 4% of patients survive 5 years following diagnosis.Here, we used inununohistochemicalan alysis to detect the intensity of RON expression in the pancreatic cancer specimens. And we analyses the relationship between the RON expression and clinicalpa thologic stages and prognosis.Methods: Resection specimens of pancreatic cancer in the department of General surgery No.3 hospital Anhui Medical University from January 2005 to May 2008, The expression of RON specimens of 31 pancreatic cancer and 31 specimens of normal pancreatic tissues adjacent to cancer and 8 pancreatic benign disease were detected by immunohistochemistry.Results: 1.RON expression in the pancreatic specimens: RON expression was observed in normal pancreatic epithelium and pancreatic cancer tissues. The levels of RON was significantly higher than those of the normal pancreatic tissues(P<0.05), suggesting that RON played an important role in tumorigenesis. 2.RON expression in pancreatic neoplasm: RON experssion became enhanced when the clinical pathologic stages elevated, and RON over-expression was correlated with aggressive tumor characteristics, such as invasive depth and lymph nodes metastasis. Suggesting that RON might influence many steps in tumor porgression and metastasis.Conclusions:1.All pancreatic tissues expressed RON and the intensity of RON expression in pancreatic tumor was much higher than in normal epithelium. 2. The expression levels of RON in pancreatic cancer tissue become enhanced when the tumor differentiation and clinical stages elevated. 3. Taken together, our findings suggest that RON receptor signaling may contribute to pancreatic carcinogenesis.