Activation of oncogene c-Ha-ras in gastric cancer of Chinese patients.
A transforming gene was cloned from a focus of rat fibroblast cell line Rat 1 transfected with DNA of a gastrocarcinoma cell line. The transforming gene is the activated form of oncogene c-Ha-ras, and the lesion was identified as a single nucleotide substitution at codon 12 by sequencing. We further used polymerase chain reaction (PCR)-restriction analysis to detect the mutations at codon 12 of c-Ha-ras. By using this method, 11 cases out of 24 solid tumors and 3 cell lines of gastric cancer were shown to contain mutations, and there was a strong correlation between mutations and metastasis and survival of the patients. The role of the activated c-Ha-ras in tumorigenesis of stomach cancer was further proved through the assay in which the malignant phenotypes of the c-Ha-ras-transformed cells were partially inhibited by blocking the c-Ha-ras expression with antisense oligonucleotides or exogenous plasmid expressing antisense RNA.
Deng
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Department of Biochemistry and Molecular Biology, Beijing Institute for Cancer Research, China.
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Xu
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Lu
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D044466:Asian People / Q000235:genetics; D001483:Base Sequence; D002681:China; D015972:Gene Expression Regulation, Neoplastic; D011905:Genes, ras; D006801:Humans; D008969:Molecular Sequence Data; D009154:Mutation; D009362:Neoplasm Metastasis; D016376:Oligonucleotides, Antisense; D009857:Oncogenes; D016133:Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000235:genetics* / Q000401:mortality; D015996:Survival Rate; D014162:Transfection; D014407:Tumor Cells, Cultured
D016376:Oligonucleotides, Antisense