Deregulated expression of a novel gene, NC33, in aflatoxin B₁ -induced rat hepatocellular carcinoma K2 cells

Abstract

Aflatoxin B₁ (AFB₁) is known to be one of the most potent hepatocarcinogens and causes hepatocellular carcinomas in various experimental animals. We have previously reported that AFB₁-induced rat hepatocellular carcinoma K2 cells over-express 14-3-3 β and c-myc genes which are the key regulators of in vitro and in vivo growth of K2 cells. Nonetheless, it has been speculated that in addition to these genes, some other genes also implicate in AFB₁ hepatocarcinogenesis, because AFB₁ induces genomic alterations. Here, we report the cloning of cDNA encoding rat nuclear protein NC33 (nuclear coiled-coil protein 33 kDa) as a new candidate responsible for AFB₁ hepatocarcinogenesis. The expression level of NC33 mRNA in K2 cells was extremely higher than that in normal rat liver. The colony forming ability of K2 cells in semi-solid medium as a hallmark of tumor cells in vitro was diminished by the down-regulation of NC33 gene expression. Thus, it is most likely that the deregulated expression of NC33 gene is involved in AFB₁ hepatocarcinogenesis.