Down-Regulation of Dehydroepiandrosterone Sulfotransferase Gene in Human Hepatocellular Carcinoma

Differential display (DD) PCR cloning of differentially expressed genes in hepatocellular carcinoma (HCC) and adjacent unaffected tissue demonstrated preferential down- regulation of a vital sex steroid precursor ( dehydroepiandrosterone sulfotransferase; DHEA-ST; SULT2A1) in HCC. SULT2A1 mRNA and/or protein expression in HCC were markedly reduced in 61 of 120 (50.8%) primary unicentric HCCs. The down-regulation was more frequent in grade III versus grade I HCC (68.1% versus 32.1%, P = 0.0025) , and in stage 3 versus stage 1 HCC (62.7% versus 29.2%, P = 0.007). The lowered expression in tumor cells of SULT2A1 in HCC tissues involved in metabolism and/or inactivation of sex steroids is consistent with a regulatory role of the SULT2A1 gene product in the development and/or tumor cell differentiation and progression of human HCC. This suggestion is partly supported by our observations that the down-regulated SULT2A1 gene expression correlated with a higher grade and stage of HCC