- 作者: Ching-Ann Liu; Mei-Jung Wang; Chin-Wen Chi; Chew-Wun Wu; Jeou-Yuan Chen
- 作者服務機構: Graduate Institute of Life Sciences, National Defense Medical Center, Institute of Biomedical Sciences, Academia Sinica, Department of Medical Research and Education and Department of Surgery, Veterans General Hospital, Taipei, Taiwan, ROC
- 中文摘要: --
- 英文摘要: Like many epithelial-derived cancers, gastric cancer(GC)results from a multistep tumorigenic process. However,the detailed mechanisms involved in GC formation arepoorly characterized. Using an ordered differential dis-play method, we have identified rhotekin(RTKN), thegene coding for the Rho effector, RTKN, as one of thegenes differentially expressed in human GC. Northernanalysis using human multiple tissue blots showed thatRTKN is predominantly expressed in the kidney and spi-nal cord, and,to a lesser degree, in the thyroid,tongue,liver, brain,prostate, trachea, and stomach. RT-PCR anal-ysis confirmed that RTKN was overexpressed in most(5/7; 71%)GC examined. By analyzing the StanfordMicroarray Database for the expression profiles of gas-tric tissues, we also found a progressional increase inRTKN expression in nonneoplastic mucosa, GC, andthen lymph node metastases(p<0.005 by Jonckheere-Terpstra test), suggesting that RTKN expression corre-lates with GC progression. The role of RTKN in the patho-genic development of GC was investigated by transfec-tion and expression of RTKN in AGS gastric cells, whichexpress endogenous RTKN at a low basal level. Flow-cytometric analysis showed that RTKN-transfected AGScells were significantly more resistant than vector-trans-fected cells to apoptosis upon treatment with sodiumbutyrate. To explore the mechanisms underlying RTKN-mediated cell survival,a reporter assay was performed.Since the NF-KB activation is known to promote cell sur-vival and Rho GTPase may lead to NF-kB activation,wetransfected AGS cells with the RTKN expression vectoralong with a pNF-KB-Luc reporter plasmid. Our resultsshowed that overexpression of RTKN induced robustactivation of NF-KB, and RTKN一mediated NF-KB activa-tion was suppressed significantly by C3 transferase, aninhibitor of the small GTPase Rho. We conclude that Rho/RTKN-mediated NF-KB activation leading to cell survivalmay play a key role in gastric tumorigenesis. This studyprovides original documentation for the overrepresenta-tion of the Rho GTPase effector rhotekin in human cancerand its links to cancer formation.
- 中文關鍵字: --
- 英文關鍵字: --