MOLECULAR-CLONING OF A NOVEL MESSENGER-RNA HIGHLY EXPRESSED IN HAEMOCHROMATOTIC HUMAN LIVER AND PROLIFERATING CELLS

Pathological changes arising in altered cell biology and diseases such as cancer are driven by changes in gene expression. In the inherited disease haemochromatotis (HC) progressive iron loading of the parenchy mal cells (hepatocytes) of the liver leads to cellular toxicity. If le ft untreated, fibrosis, cirrhosis and ultimately liver cancer occur. B y using differential display reverse transcriptase polymerase chain re action (DDRT-PCR) techniques, we have identified and isolated several differentially displayed mRNAs that are excessively expressed or repre ssed in HC liver compared to normal human liver. One of these mRNAs wa s found to be strongly expressed in the liver of a patient with HC and in tumour tissue from a subject with hepatocellular carcinoma complic ating HC (HC/HCC). The message of this gene was detected at a very low level in normal human liver. Northern analysis showed that this gene is also expressed in lymphocytes of HC patients and in MOLT-4 human T- lymphoid cells irrespective of iron status. The partial 1.0 kb cDNA se quence of the 9.5 kb transcript of this gene is unique and we propose that this gene may be related to cell proliferation and HC/HCC human l iver. (C) 1996 Academic Press, Inc.