| Co-Investigator(Kenkyū-buntansha) |
KUNIAYSU Hiroki Hiroshima University School of Medicine, Department of Pathology, Assistant, 医学部, 助手 (00253055)
YOKOZAKI Hiroshi Hiroshima University School of Medicine, Department of Pathology, Assistant Prof, 医学部, 講師 (10200891)
YASUI Wataru Hiroshima University School of Medicine, Department of Pathology, Associate Prof, 医学部, 助教授 (40191118)
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| Research Abstract |
Gene changes in multiple oncogenes, multiple suppressor genes and genetic instability may be implicated in stomach carcinogenesis. Among them, aberrant expression and amplification of the c-met gene, inactivation of the p53 gene and CD44 abnormal transcripts are common events of both well differentiated type and poorly differentiated type gastric cancers. Amplification of the cyclin E gene is also observed in gastric cancer regardless of histological types. Decreased expression and mutations of the pic1 (p21) gene occurs independent of the p53 mutations. In addition, K-ras mutations, c-erbB-2 gene amplification, loss of heterozygosity (LOH) and mutations of the APC gene, LOH of the bcl-2 gene, and LOH at DCC locus are preferentially associated with well differentiated type gastric cancer. Precancerous lesions including hyperplastic polyp, intestinal metaplasia and adenoma also show genetic changes which are found in well differentiated type cancer. Conversely, genetic instability may be involved in the first step of stomach carcinogenesis for poorly differentiated type. Reduction or loss of cadherin and catenins, K-sam gene amplification, and c-met gene amplification are necessary for the development and progression of poorly differentiated type or scirrhous carcinoma.
Interaction between cell-adhesion molecules in the c-met expressed tumor cells and hepatocyte growth factor from stromal cells is involved in the morphogenesis of two types of gastric cancer. Taken together, different genetic pathways of stomach carcinogenesis may exist for well differentiated and poorly differentiated gastric cancers. Some of the former may develop by a cumulative series of gene alterations similar to those of colorectal cancer.
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