Suppression of protein kinase C and the stimulation of glucocorticoid receptor synthesis by dexamethasone in human fibroblasts derived from tumor tissue

Preston Gadson, Judy McCoy, Ann Charlotte Wikström, Jan-Ake Gustafsson

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Exposure of fibroblasts derived from keloid tissues, desmoid and dermal tissue from individuals with Gardner's syndrome (GS) to dexamethasone resulted in the suppression of protein kinase C (PKC) activity and [3H]thymidine incorporation into DNA, and a 20-fold induction of glutamine synthetase activity. Treatment of GS and keloid fibroblasts with 0.1 μM dexamethasone for 36 h increased glucocorticoid receptor (GR) synthesis, as determined by [35S]methionine labeling and immunoprecipitation with a monoclonal antibody to the human GR. The suppression of PKC activity by dexamethasone was shown to result from a loss of protein mass as determined by immunoblotting using an antibody to PKC type III. In contrast to these results, exposure of fibroblasts isolated from normal tissues to dexamethasone did not result in the suppression PKC and [3H]thymidine incorporation, there was only a sixfold induction of glutamine synthetase, and a decrease of GR synthesis. As no primary receptor binding defect could be detected, the altered response of tumor cells to steroid-occupied receptor indicates a partial post-receptor binding defect in GS and keloid cells.

Original languageEnglish (US)
Pages (from-to)185-198
Number of pages14
JournalJournal of Cellular Biochemistry
Volume43
Issue number2
DOIs
StatePublished - Jan 1 1990

Keywords

  • dexamethasone
  • fibroblast
  • glucocorticoid
  • protein kinase C
  • tumor tissue

ASJC Scopus subject areas

  • Biochemistry
  • Cell Biology

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