HCC CKs are altered histones during tumor transformation in hepatoma

The stability of cytokeratin (CK) protein during tumor transformation in human hepatocellular carcinoma (HCC) was studied with molecular approach previously. The results demonstrated that the CK was modulated in human HCC. Besides this, three low molecular weight CK molecules (named HCC CK) were found. It indicated that these HCC CKs are undergone modulation from human hepatocyte CK18. However, there were many differences between the CK18 and HCC CK. First, the antigenecity of HCC CK had been changed since they could not be recognized by CAM5.2 antibody on Western blot. Second, the sequences of N-terminal residues of HCC CK were matched with those of the N-terminal residues of human histone. In this study, we confirmed that the HCC CK was actually to be histones because they reacted to anti-histone antibody on Western blot. Furthermore, we found that the histones of human HCC had been changed during the process of tumor transformation since they could be co-immunoprecipitated with CK18 and could be detected by Western blot while this phenomenon did not happen in the normal liver tissue. We also found that not all histones change in human HCC. Only H3 was detected on Western blot while H1, H2A, H2B, and H4 were not detected in human HCCs.