Altered expression of the growth and transformation suppressor PML gene in human hepatocellular carcinomas and in hepatitis tissues.

Abstract

The promyelocytic leukaemia (PML) gene, which encodes a transformation and growth suppressor, was first identified at a chromosomal translocation break point in acute promyelocytic leukaemia. To elucidate if PML may be involved in hepatocellular carcinoma (HCC), the expression of PML was analysed using immunohistochemistry in human HCC and hepatitis tissues. Our studies demonstrated overexpression of PML protein in the PML-oncogenic domain (POD) structure in 50% of HCC (11/22). Enhanced expression and cytoplasmic localisation of PML was associated with cirrhosis. Increased expression of PML was also found in liver abscesses. However, in colon metastasis to the liver, the expression of PML was moderate to low, although strong expression was seen in the surrounding interstitial cells, macrophages and lymphocytes, an indication of the inflammation process associated with tumour growth. Most interestingly, strong expression of PML was found in neoplastic cells at the periphery of the tumours, but progressively decreased in cells at the centre of the tumours, which may be associated with an altered transform phenotype or apoptosis. The altered expression of PML indicates that this nuclear protein may play an important role in cellular response to stress and inflammation, as well as in compensatory cell growth.