GENE-EXPRESSION REGULATION FOR INTERFERON-ALPHA IN HEPATOCELLULAR-CARCINOMA

We investigated whether regulation of interferon-alpha gene expression could be involved in liver tumor biology an the role, if any, of hepa titis B virus in the regulation of tumor cytokine gene expression. Gen e expression was investigated at the transcriptional level using 'in s itu' hybridization of cytokine message with an interferon-alpha cDNA p robe and at the translational level with immunohistochemistry using an immunoperoxidase technique. Compared to histologically normal liver, a greater percentage of tumor and non-tumor-involved liver tissue sect ions (67-80% vs. 17%) contained cells positive for interferon-alpha me ssenger RNA, many of which were also seen to contain an increased numb er of transcripts (> 100 grains/cell). Hepatitis B infection did not a ppear to play a role in gene activation, at the hepatocellular level, in liver disease. Except for sinusoidal cells, cells containing cytoki ne transcripts also produced mature immunoreactive protein. Absence of interferon-alpha protein within mononuclear and sinusoidal cells in s eronegative hepatocellular carcinoma tissue with/without underlying li ver disease suggested deficient cytokine gene expression, at the post transcriptional level, within these cells in this group. Bile duct epi thelia in tumor tissue were found to contain immunoreactive protein fo r interferon-alpha. In summary our results suggest that interferon-alp ha gene activation in hepatocellular carcinoma occurs as a result of t he liver cell damage and does not play a dominant role in tumor biolog y.