title: Control of the expression of c-sis mRNA in human glioblastoma cells by phorbol ester and transforming growth factor beta 1.
abstract: The regulation of c-sis oncogene expression in human glioblastoma cell line A172 has been investigated using a sensitive RNA-RNA solution hybridization method. Enhanced expression of c-sis mRNA was induced by phorbol ester (PMA) and diacylglycerol, each of which activates protein kinase C. c-sis mRNA was also induced by transforming growth factor beta (TGF-beta). The response to PMA and TGF-beta was transient, and in each case the decrease in c-sis mRNA level following maximum stimulation occurred with a half-life similar to the mRNA half-life previously determined. Cycloheximide had no significant effect on the induction of c-sis mRNA by either PMA or TGF-beta. The increases in c-sis mRNA following addition of either PMA or TGF-beta correlated well with increases in c-sis transcription as observed by the nuclear run-on technique. In cells in which protein kinase C had been down-regulated, there was no inhibition of the c-sis mRNA response to TGF-beta. Furthermore in cells pretreated with TGF-beta, induction by PMA was unaffected. Thus the TGF-beta signal pathway does not involve activation of protein kinase C, and at least two initially distinct intracellular signaling routes lead to activation of c-sis gene expression in this glioblastoma cell line. The protein kinase inhibitor H7 abolished the ability of not only PMA but also of TGF-beta to induce c-sis mRNA. The ability of H7 to inhibit the TGF-beta stimulation suggests that a protein kinase other than protein kinase C is involved in the signal transduction by TGF-beta.
authors.affiliation: Department of Biochemistry, Case Western Reserve University, Cleveland, Ohio 44106.
authors.forename: R D
authors.initials: RD
authors.lastname: Press
authors.forename: A
authors.initials: A
authors.lastname: Misra
authors.forename: G
authors.initials: G
authors.lastname: Gillaspy
authors.forename: D
authors.initials: D
authors.lastname: Samols
authors.forename: D A
authors.initials: DA
authors.lastname: Goldthwait
mesh_terms: D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D004789:Enzyme Activation; D005786:Gene Expression Regulation / Q000187:drug effects*; D005910:Glioma / Q000235:genetics*; D006801:Humans; D007546:Isoquinolines / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology; D010982:Platelet-Derived Growth Factor / Q000378:metabolism*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger / Q000096:biosynthesis*; D012334:RNA, Neoplasm / Q000096:biosynthesis*; D013997:Time Factors; D014158:Transcription, Genetic / Q000187:drug effects; D015291:Transforming Growth Factors / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D007546:Isoquinolines; D010703:Phorbol Esters; D010879:Piperazines; D010982:Platelet-Derived Growth Factor; D011518:Proto-Oncogene Proteins; D020574:Proto-Oncogene Proteins c-sis; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D015291:Transforming Growth Factors; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011493:Protein Kinase C