Control of the Expression of c-sis mRNA in Human Glioblastoma Cells by Phorbol Ester and Transforming Growth Factor β

Richard D. Press, Anita Misra, Glenda Gillaspy, David Samols, David A. Goldthwait

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24 Scopus citations

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 β (TGF-β). The response to PMA and TGF-β 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-β. The increases in c-sis mRNA following addition of either PMA or TGF-β 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-β. Furthermore in cells pretreated with TGF-β, induction by PMA was unaffected. Thus the TGF-β 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-β to induce c-sis mRNA. The ability of H7 to inhibit the TGF-β stimulation suggests that a protein kinase other than protein kinase C is involved in the signal transduction by TGF-β.

Original languageEnglish (US)
Pages (from-to)2914-2920
Number of pages7
JournalCancer Research
Volume49
Issue number11
StatePublished - Jun 1 1989

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Press, R. D., Misra, A., Gillaspy, G., Samols, D., & Goldthwait, D. A. (1989). Control of the Expression of c-sis mRNA in Human Glioblastoma Cells by Phorbol Ester and Transforming Growth Factor β. Cancer Research, 49(11), 2914-2920.