Glucocorticoid modulation of transformed cell proliferation is oncogene specific and correlates with effects on c-myc levels

M. Kerry O'Banion, Richard M Levenson, Ute G. Brinckmann, Donald A. Young

Research output: Contribution to journalArticle

12 Scopus citations

Abstract

In the presence of the glucocorticoid hormone dexamethasone, bovine papillomavirus-1 (BPV-1)-transformed C127 mouse fibroblasts assume a flattened morphology and reach a saturation density of only 50% of that attained without hormone. This phenotypic reversion of transformation is dependent on the continued presence of dexamethasone and occurs with concentrations as low as 1 nM. Dexamethasone also suppresses the growth of the parental C127 cells as well as that of cells transformed by polyoma middle-T. In contrast, the growth of C127 cells transformed by the oncogenes v-H-ras, v-mos, or v-fes is inhibited by low concentrations of dexamethasone (1 nM) and stimulated by higher concentrations (0.1-1 μM), possibly due to dexamethasone-induced transcription from the viral long terminal repeat promoters as is shown for v-H-ras. On the other hand, inhibition of BPV-transformed cell line growth by dexamethasone does not appear to be related to hormone effects on BPV-1 oncogene transcription. Indeed, in several cases, dexamethasone increases the steady state transcript levels of the BPV-1 oncogenes, E5 and E6-E7, while suppressing cellular proliferation. Dexamethasone also rapidly reduces the steady state levels of c-myc in the BPV-transformed cells but has less effect on c-myc expression in the ras-transformed cells. These results demonstrate that the growth-promoting actions of the papillomavirus transforming genes, but not those of several retroviral oncogenes, may be overcome by dexamethasone, which appears to act by down-regulation of c-myc expression.

Original languageEnglish (US)
Pages (from-to)1371-1380
Number of pages10
JournalMolecular Endocrinology
Volume6
Issue number9
StatePublished - 1992
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Endocrinology, Diabetes and Metabolism

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