CANCER-ASSOCIATED EXPRESSION OF GLYCOLIPID SULFOTRANSFERASE GENE IN HUMAN RENAL-CELL CARCINOMA-CELLS

Human renal cell carcinoma (RCC) tissue and a cell line derived theref rom, SMKT-R3, showed markedly increased glycolipid sulfotransferase [c erebroside sulfotransferase (CST); EC 2.8.2.11] activity and accumulat ed sulfoglycolipids. Recently, we cloned a human CST cDNA from a SMKT- R3 cDNA library (K. Honke et at, J. Biol. Chem., 272: 4864-4868, 1997) . In this study, se investigated the expression of the CST gene in sev en human RCC lines (SMKT-R1, SMKT-R2, SMKT-R3, SMKT-R4, TOS-1, TOS-2, and ACHN) and their normal counterpart, human renal proximal tubular c ells. On Northern blot analysis, a marked increase of CST mRNA was obs erved in every RCC line, except for ACHN, as compared with normal cell s. ACHN cells showed a slightly increased level of CST mRNA. CST activ ity was correlated with the amount of mRNA. Sulfoglycolipid analysis r evealed that expression of lactosylceramide sulfate was correlated wit h the CST level. Furthermore, we examined the effects of epidermal gro wth factor (EGF), tetradecanoylphorbol-13-acetate, and genistein, whic h are known to regulate CST activity in SMKT-R3 cells, on CST-gene exp ression in various RCC cells. On treatment with EGP, CST mRNA time-dep endently increased in accord with its activity in SMKT-R3 cells. Yet, augmentation by EGF was only observed in SMKT-R3. In contrast, a reduc tion of CST mRNA and activity by tetradecanoylphorhol-13-acetate and g enistein was observed in all of the lines examined. Taken together, th ese findings indicate that in human RCC cells, the CST gene is general ly overexpressed via a signaling pathway involving protein kinase-C an d tyrosine kinases.