Human
renal cell carcinoma (RCC) tissue and a cell line derived therefrom, SMKT-R3, showed markedly increased
glycolipid sulfotransferase [
cerebroside sulfotransferase (CST); EC 2.8.2.11] activity and accumulated
sulfoglycolipids. Recently, we cloned a human CST
cDNA from a SMKT-R3 cDNA library (K. Honke et al., J. Biol. Chem., 272: 4864-4868, 1997). In this study, we investigated the expression of the CST gene in seven 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 cells. On Northern blot analysis, a marked increase of CST
mRNA was observed in every RCC line, except for ACHN, as compared with normal cells. ACHN cells showed a slightly increased level of CST
mRNA. CST activity was correlated with the amount of
mRNA. Sulfoglycolipid analysis revealed that expression of
lactosylceramide sulfate was correlated with the CST level. Furthermore, we examined the effects of
epidermal growth factor (
EGF), tetradecanoylphorbol-13-acetate, and
genistein, which are known to regulate CST activity in SMKT-R3 cells, on CST-gene expression in various RCC cells. On treatment with
EGF, CST
mRNA time-dependently increased in accord with its activity in SMKT-R3 cells. Yet, augmentation by
EGF was only observed in SMKT-R3. In contrast, a reduction of CST
mRNA and activity by tetradecanoylphorbol-13-acetate and
genistein was observed in all of the lines examined. Taken together, these findings indicate that in human RCC cells, the CST gene is generally overexpressed via a signaling pathway involving
protein kinase-C and
tyrosine kinases.