Overexpression of 14-3-3.BETA. gene and its role in aflatoxin B1-induced hepatocellular carcinoma cells.
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We have previously reported that 14-3-3β mRNA was overexpressed as well as c-mycmRNA in aflatoxin B<SUB>1</SUB> (AFB<SUB>1</SUB>)-induced rat hepatoma K1 and K2 cells as compared with that of the normal liver tissue. 14-3-3β protein is known to play an important role in cell growth and differentiation through the binding to signal transduction factors. Here we report that the protein level of 14-3-3β expression was also significantly increased in K1 and K2 cells. Southern blot analysis demonstrated that some genetic changes including point mutation were caused in 14-3-3β gene locus, because different hybridization patterns were observed among the normal rat liver, K1 and K2 DNAs, when digested with Eco RI, Bam HI or Pst I. The addition of antisense 14-3-3β oligodeoxynucleotides (ODNs) reduced the growth rate of K2 cells. PCR-single-strand conformation polymorphism (SSCP) analysis of ras family genes including H-, K-and N-ras revealed that any mutations leading to oncogenic activity were not detected in both cells. These results suggest that the mutational activation of 14-3-3β gene expression, but not ras family genes, plays an important role in AFB<SUB>1</SUB> hepatocarcinogenesis together with the deregulated expression of c-rnyc gene.
- 日本マイコトキシン学会の論文
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