| Background and AimColorectal cancer (CRC) is one of the increasing malignant tumors in China. CRC typically develops over decades and involves multiple genetic events during carcinogenesis. This has led to the development of a multistep model of colorectal tumorigenesis. It is generally believed that one of initiating steps in colorectal carcinogenesis is mutation in stem cell or its early progenitor cells.There is strong evidence to suggest that microcystin pollution and Helicobacter pylori (H.pylori) infection may contribute to the tumorigenesis from the etiological study of CRC in prevalence region. Microcystin pollution and H.pylori infection are likely important pathogenic factors in China. Microcystin, a main group of the cyanotoxins is mainly retained within the producer cells during cyanobacterial bloom development and are released into surrounding medium such as water by senescence and lysis of the blooms. It has been confirmed that microcystins were potent inhibitors of serine/threonine protein phosphatase (PPs) types 1, 2a and tumor promoters in laboratory animals and may be involved with promotion of primary liver cancer in humans. The tumour-promoting activity of MC is likely to arise from its ability to potently inhibit PP2A which regulates several mitogen-activated protein kinases (MAPK). Microcystin activates a variety of protein kinases possibly byactivating the MAPK cascade via tyrosine kinase-linked G protein receptors which would in turn activate phospholipase C (PLC) .However, some studies also showed that microcystins may relate to the carcinogenesis of gastrointestinal tract. But the mechanism of microcystin in colorectal cancer keeps unclear by far. Further understanding of the role of microcystin during carcinogenesis might facilitate the development of a new therapeutic and preventive strategy for colorectal carcinoma.Recently some oncogenic bacteria such as H.pylori have been recognized as the causative agent of human cancers. H.pylori, particularly with strains positive for CagA protein, may also increase the risk of mucosa-associated lymphoid tissue (MALT) lymphoma and gastric adenocarcinoma. Studies have explored the possible association between H. pylori infection and colorectal cancer and concluded CagA in H. pylori-infected affected risk for colorectal cancer. Type I isolates of H. pylori possess a major disease-associated genetic component, the cag pathogenicity island (PAI) which encodes a type IV secretion apparatus and virulence factors such as the immunodominant CagA protein. CagA is translocated from the bacterium into the host cell by specific IV secretion apparatus. The C-terminal half of the CagA is phosphorylated in tyrosine sites by c- src/lyn protein kinase family once translocated into eukaryotic cells and a src homology 2 (SH2)-containing tyrosine phosphatase 2 (SHP-2) is an intracellular target of CagA protein. SHP-2 is an important adaptor molecule in several cell signal transductions. Phosphorylated CagA disturbs signal transduction by binding with SHP-2 and Grb2 molecules in host cell. However, CagA protein varies in size in different strains, this size variation raises an intriguing possibility that the biological activity of CagA can vary from one strain to the next, which may influence the pathogenicities of different strains. China is one of nations where the infection incidence of H.pylori are among the highest in the world and more than 90% isolated strains possessed PAI gene, the biological activity of the H. pylori virulence factor CagA isolated in China remains unclear so far. Epithelial stem cells reside near the base of each crypt and divide to produce daughter cell, which migate up towards the crypt mouth. These daughter cells, known as transit amplifying, proliferate rapidly and differentiate. Each crypt is derived ultimately from a single stem cell though there may be more than one functional stem cell. CRCoriginated from carcinogenesis of stem cell.The aim of the study is to explore whether microcystin and/or H.pylori CagA...
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