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PMID: 8440743 Published · ppublish English Editorial

Molecular mechanism of stomach carcinogenesis.

Journal of cancer research and clinical oncology ·Vol. 119 ·No. 5 ·1993-00-00 ·Pages 265-72

Tahara E

Abstract

Gene changes in multiple oncogenes, multiple growth factors and multiple tumor-suppressor genes are observed in stomach cancer. Among them, those most commonly implicated in both well-differentiated adenocarcinoma and poorly differentiated adenocarcinoma are inactivation (mutations and allele loss) of the p53 gene, and activation (abnormal expression and amplification) of the c-met gene. Moreover, they occur at an early stage of stomach carcinogenesis. In addition, loss of heterozygosity (LOH) on chromosome 5q (APC locus) is frequently associated with well-differentiated adenocarcinoma. LOH on chromosome 18q (DCC locus) and LOH of the bcl-2 gene also are common events of well-differentiated adenocarcinoma. LOH on chromosomes 1q and 7q may be involved in the progression of well-differentiated adenocarcinoma. Conversely, the development of poorly differentiated adenocarcinoma, in addition to changes in p53 and c-met genes, requires reduction or dysfunction of cadherin. Overexpression of bcl-2 protein is observed in poorly differentiated adenocarcinoma or signet-ring cell carcinoma. Moreover, the K-sam gene is amplified preferentially in poorly differentiated adenocarcinoma of scirrhous carcinoma. K-sam amplification in scirrhous carcinoma often occurs independently of c-met gene amplification. LOH on chromosome 1p also is relatively common in poorly differentiated adenocarcinoma. Exceptionally, signet-ring cell carcinoma shares APC mutations. There are some differences in expression of the growth-factor/receptor system between well-differentiated adenocarcinoma and poorly differentiated adenocarcinoma. Moreover, interaction between cell-adhesion molecules in tumor cells expressing c-met and hepatocyte growth factor (HGF) from stromal cells is linked with morphogenesis of two histological types of stomach cancer. Intestinal metaplasia and adenoma of the stomach also contain p53 mutations and K-ras mutations or tpr-met rearrangement. Taken together, different genetic pathways of stomach carcinogenesis may exist for poorly differentiated and well-differentiated stomach cancers. Some of the latter may develop by a cumulative series of gene alterations similar to those of colorectal cancer.

Related Genes
APC DCC H-ras IL-1&agr K-ras K-sam bek c-erbB-2 c-met cripto p53
MeSH Terms
Humans Stomach Neoplasms/etiology,genetics
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Tahara E
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Article Info
Journal
Journal of cancer research and clinical oncology
Abbr.
J Cancer Res Clin Oncol
ISSN
0171-5216
DOI
10.1007/BF01212724
Published
1993-00-00
Pages
265-72
Language
English
Region
Germany
NLM ID
7902060
Subset
IM
External Links
PubMed source DOI: 10.1007/BF01212724 View journal details
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