[Alteration of genomic structure and/or expression of cancer associated genes in hepatocellular carcinoma].
Cancer is thought to arise from the accumulation of several genetic mutations in a single cell. These include integration of viral genomes, activation of protooncogenes and inactivation of tumor suppressor genes. HCC is one of the most common cancers in Asia and Africa. Various studies have revealed its association with hepatitis B or C viral infection. While activation of known protooncogenes, such as ras genes does not seem to play an important role, frequent allelic loss on specific chromosomal arms, 4q, 13q, 16q and 17p, indicates that dysfunction of diverse tumor suppressor genes located on these chromosome arms is involved in the development of HCC. An informative p53 mutational spectrum of frequent G to T transversions in codon 249 is found in HCCs from either Qidong, People's Republic of China, or southern Africa. This observation links exposure to aflatoxin B1, a known cancer risk factor in these geographic regions. Recently, we found that expression of syndecan-1, which is a transmembrane heparan sulfate proteoglycan involved in cell matrix interactions and growth factor bindings, was inversely associated with metastatic potential in human hepatocellular carcinoma as like nm23-H1 expression was. Transfection with syndecan-1 gene suppresses invasive activity of hepatoma cells. These data support our hypothesis that syndecan-1 is one of important metastasis suppressor factors in hepatoma cells. PR-39 is a proline-rich antimicrobial peptide which was isolated from a pig small intestine and has been reported to induced syndecan-1 on mouse mesenchymal cells. Transfection with PR-39 gene caused induction of syndecan-1 and altered invasive phenotype and actin structure on hepatoma cells. Syndecan-1 and PR-39 may serve as a basis for design of drug or gene therapy effective against metastasis of hepatocellular carcinomas.
Fujimoto
Y
Y
Third Department of Internal Medicine, Asahikawa Medical College.
Kohgo
Y
Y
D000595:Amino Acid Sequence; D000818:Animals; D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D006528:Carcinoma, Hepatocellular / Q000235:genetics*; D016158:Genes, p53 / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D008562:Membrane Glycoproteins / Q000235:genetics / Q000502:physiology; D051379:Mice; D008969:Molecular Sequence Data; D020559:Monomeric GTP-Binding Proteins; D009154:Mutation; D054778:NM23 Nucleoside Diphosphate Kinases; D009701:Nucleoside-Diphosphate Kinase; D010455:Peptides / Q000235:genetics; D011509:Proteoglycans / Q000235:genetics / Q000502:physiology; D013552:Swine; D053668:Syndecan-1; D053667:Syndecans; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D008562:Membrane Glycoproteins; D054778:NM23 Nucleoside Diphosphate Kinases; D010455:Peptides; D011509:Proteoglycans; C508241:SDC1 protein, human; C508242:Sdc1 protein, mouse; D053668:Syndecan-1; D053667:Syndecans; D014157:Transcription Factors; C072212:PR 39; C517938:NME1 protein, human; C517939:Nme1 protein, mouse; D009701:Nucleoside-Diphosphate Kinase; D020559:Monomeric GTP-Binding Proteins