Regulation of activity levels of glycolipid sulfotransferases by transforming growth factor alpha in renal cell carcinoma cells.
Accumulation of sulfolipids associated with markedly elevated levels of glycolipid sulfotransferase activities was previously demonstrated in human renal cell carcinoma cells. To explore the regulation mechanisms of sulfoglycolipid synthesis in renal cancer, effects of various growth factors on the metabolic enzymes of sulfoglycolipids were investigated by using a human renal cell carcinoma cell line, SMKT-R3. Among the growth factors tested, transforming growth factor alpha (TGF-alpha) and epidermal growth factor (EGF) were found to increase the sulfotransferase activity markedly (about 300%), but did not change that of arylsulfatase A, which hydrolyzes sulfoglycolipids. The augmented effects of TGF-alpha was abolished by cycloheximide. Since TGF-alpha is known to bind to the same receptor as EGF, SMKT-R3 cells were investigated for the EGF receptor by affinity cross-linking with 125I-EGF. A radiolabeled protein with a molecular mass of 175 kDa corresponding to the ligand-receptor complex was immunoprecipitated with a monoclonal anti-EGF receptor antibody. When production of the growth factors was examined immunochemically, the cells were found to secrete TGF-alpha at a low level and retain it in a membrane-bound form, whereas EGF was not detected. These observations suggest that the sulfotransferase activities are regulated through the autocrine, paracrine, and/or juxtacrine modes of intercellular stimulation by TGF-alpha in human renal cancer cells.
Kobayashi
T
T
Biochemistry and Virology Laboratory, Hokkaido University School of Medicine, Sapporo, Japan.
Honke
K
K
Gasa
S
S
Imai
S
S
Tanaka
J
J
Miyazaki
T
T
Makita
A
A
D002292:Carcinoma, Renal Cell / Q000201:enzymology* / Q000378:metabolism; D002553:Cerebroside-Sulfatase / Q000378:metabolism; D004789:Enzyme Activation / Q000187:drug effects; D066246:ErbB Receptors / Q000032:analysis; D006801:Humans; D007680:Kidney Neoplasms / Q000201:enzymology* / Q000378:metabolism; D015238:Sulfotransferases / Q000378:metabolism*; D016211:Transforming Growth Factor alpha / Q000096:biosynthesis / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
D016211:Transforming Growth Factor alpha; D066246:ErbB Receptors; D015238:Sulfotransferases; C020556:galactosylceramide sulfotransferase; D002553:Cerebroside-Sulfatase