Hepatocarcinogesis and Genomic Instability: Functional Analysis of Y-box binding protein.

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We isolated dbpA, a member of the Y-box binding protein family, as the candidate for the cellular protein inducing genomic instability. We obtained the following findings about dbpA.1.DbpA expressed in E.coli showed the weak strand exchange activity. Recently, YB-i, another member of this family, is reported to have the annealing activity of DNA or RNA (JBC 276 : 4484 1-44847), and the possible association of this family with DNA recombination is suggested by their work as well as by ours.2.We raised anti-dbpA Ab which recognized dbpA expressed in E.coli with high sensitivity. At present, we are examining the expression of dbpA in various cancer tissue. (In the level of transcripts, the enhanced expression is already confirmed in HCC.)3.We made Transgenic mouse where dbpA is. to be overexpressed in liver. We are going to examine its susceptibility to HCC.4.Using anti-YB-l Ab, we checked its expression in various human tissues. Enhanced expression was detected in several normal tissues including gastrointestinal epithelium, as well as in HCC.5.By replacing T with G at nt -5 of dbpA promoter region, the promoter activity increased twofold. The identical replacement was detected in 3 of 51 HCC cases. We detected the 25 kDa cellular protein which specifically bind to the promoter region with T to A conversion, and currently on the way to identify it.