3 newly discovered ERK pathway proteins related to CagA induced disease

Cytotoxin-associated gene A protein (CagA) from type I H.pylori has been proved by epidemiological and experimental studies to be closely associated with the H.pylori induced gastric diseases, especially gastric cancer. However, the precise role of CagA in cell function after H. pylori infection remains unclear and no study on exploring the global protein expression pattern which can reflect host cells response to CagA has been reported.

A research article to be published on January 28, 2008 in the World Journal of Gastroenterology addresses this question. The research team led by Prof. Zheng from Cancer Institute of Zhejiang University used ProteinChip platform, which is based on surface enhanced laser desorption / ionization time-of-flight mass spectrometry (SELDI-TOF-MS) technology, to study the global protein expression changes in AGS cells transfected with CagA gene. As various researches indicated a relationship among CagA, ERK/MAPK pathway activation and gastric cancer, the article further investigate the relationship of these protein expression differences and activation of ERK pathway by adding specific mitogen-activated protein kinase kinase (MEK) inhibitor during transfection.

When 16 proteins showed expression differences after CagA transfection, three proteins with molecular weights of 4 229, 8 162 and 9 084 Dalton were found have no expression differences under the treatment of MEK inhibitor, indicating they are downstream molecules of ERK1/2 in ERK/MAPK signaling pathway. Matching information from Swiss-Prot/TrEMBL database indicates these three proteins may be related with cell apoptosis, cell antimicrobial defense, chemotactic function, cell proliferation, differentiation and carcinogenesis, and therefore have great potential to be identified as cancer-associated proteins in further research.

Due to the high sensitivity and resolution in low molecular weight range of SELDI-ProteinChip technology, biomarkers discovered in this study are mainly low mass range and/or low abundance disease related proteins, which are difficult to detect by traditional methods. These results demonstrate a new view of molecules involved in the CagA related signaling pathways, and thus may provide new targets for further understanding of the biological function of CagA and new therapeutic targets.

Reference: Ge Z, Zhu YL, Zhong X, Yu Jk, Zheng S. Discovering differential protein expression caused by CagA-induced ERK pathway activation in AGS cells using the SELDI-ProteinChip platform. World J Gastroenterol 2008; 14(4): 554-562
http://www.wjgnet.com/1007-9327/14/554.asp

Correspondence to: Professor Shu Zheng, 88 Jiefang Road, Cancer Institute of Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, Zhejiang, China. zhengshu@zju.edu.cn
Telephone: +86-571-87784501 Fax: +86-571-87214404

World Journal of Gastroenterology (WJG), a leading international journal in gastroenterology and hepatology, has established a reputation for publishing first class research on esophageal cancer, gastric cancer, liver cancer, viral hepatitis, colorectal cancer, and H pylori infection and provides a forum for both clinicians and scientists. WJG has been indexed and abstracted in Current Contents/Clinical Medicine, Science Citation Index Expanded (also known as SciSearch) and Journal Citation Reports/Science Edition, Index Medicus, MEDLINE and PubMed, Chemical Abstracts, EMBASE/Excerpta Medica, Abstracts Journals, Nature Clinical Practice Gastroenterology and Hepatology, CAB Abstracts and Global Health. ISI JCR 2003-2000 IF: 3.318, 2.532, 1.445 and 0.993. WJG is a weekly journal published by WJG Press. The publication dates are the 7th, 14th, 21st, and 28th day of every month. WJG is supported by The National Natural Science Foundation of China, No. 30224801 and No. 30424812, and was founded with the name of China National Journal of New Gastroenterology on October 1, 1995, and renamed WJG on January 25, 1998.