癌症是全球重大死因之一，而膀胱癌是最為常見的泌尿道癌症，其中又以移形上皮細胞癌占了百分之九十之多。酪胺酸磷酸激酶接受器是一種主要的致癌基因，並且在癌化的過程中扮演著重要的腳色，例如: 細胞生長; 爬行; 貼附; 及變性。然而，一旦這些酪胺酸磷酸激酶接受器接受到其配體的刺激，就會形成雙聚合的現象。RON是屬於致癌基因-MET家族的成員之一，並且已有許多研究已經支持RON參與上皮細胞癌化。首先，我們實驗室建立會大量表現RON的細胞株JR，並且利用晶片分析找出與RON大量表現相關的基因。在這些基因當中，我們選擇一種血球表面抗原LU作為更深入的研究方向。再從 RT-PCR的實驗中知道，當RON大量表現的時候，LU確實也是會有高度表現的現象，這個結果和晶片分析是相符合的。另外，我們也證明RON和LU會彼此交互作用，並且都同樣坐落在細胞膜上。利用siRNA轉殖的技術，們也證明LU會參與RON所造成的癌化過程，例如: 細胞生長， 爬行， 和貼附。所以抑制RON和LU之間的交互作用，可能可以在癌症治療上成為相當好的標的。

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.

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