The biologic significance of cross-talk between RON and Lutheran blood group antigen in human bladder cancer

• Main Authors: Hsing-Ta Chen, 陳星達
• Other Authors: Hsiao-Sheng Liu
• Format: Others
• Language: en_US
• Published: 2007
• Online Access: http://ndltd.ncl.edu.tw/handle/33812433050465158298

碩士 === 國立成功大學 === 分子醫學研究所 === 95 === Human cancer is the most important cause of death in the world, and bladder cancer is a common urologic cancer. Transitional cell carcinoma (TCC) is the major histopathology in more then 90% of these tumors. Receptor tyrosine kinases (RTKs) are a major class of proto-oncogenes, and play a crucial role in many cell regulatory processes, such as proliferation, migration, adhesion, and cellular transformation. Dimerization of the receptor proteins is an important regulatory mechanism in activation of RTKs in response to ligand stimulation. In addition, heterodimerization allows cross-talk between different receptor subfamily members. RON (recepteur d'origine nantais) belongs to MET proto-oncogene family. A number of prior studies have demonstrated its significance as an oncogene in the progression of epithelial cancer. This study was designed to identify the novel mechanisms involved in RON-related bladder carcinogenesis. We first established a RON- overexpression stable cell line (JR), and then submitted for microarray profiling analysis. Among genes associated with RON overexpression, Lutheran blood group antigen (LU) was chosen for further investigtion. The RT-PCR screening revealed that Lu is up-regulated by human RON, consistent with prediction by microarray. We then demonstrated that RON can interact with LU and co-localize at cell membrane. Using siRNA transfection, we proved that LU may involve in RON-mediated tumorigenesis, such as cell proliferation, adhesion, and migration. Taken together, our data suggest that cross-talk between RON and LU could be an optimal targeting therapy for human bladder cancer.