Glucocorticoid modulation of transformed cell proliferation is oncogene specific and correlates with effects on c-myc levels.
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 microM), 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.
O'Banion
M K
MK
Department of Medicine, University of Rochester School of Medicine and Dentistry, New York 14642.
Levenson
R M
RM
Brinckmann
U G
UG
Young
D A
DA
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000502:physiology; D001483:Base Sequence; D052688:Bovine papillomavirus 1 / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D002461:Cell Line, Transformed / Q000187:drug effects*; D002472:Cell Transformation, Viral; D003260:Contact Inhibition; D003864:Depression, Chemical; D003907:Dexamethasone / Q000494:pharmacology*; D005347:Fibroblasts / Q000187:drug effects / Q000648:ultrastructure; D015967:Gene Expression Regulation, Viral; D005813:Genes, Synthetic; D008325:Mammary Neoplasms, Experimental; D051379:Mice; D008969:Molecular Sequence Data; D009857:Oncogenes; D011120:Polyomavirus / Q000235:genetics; D011401:Promoter Regions, Genetic; D016271:Proto-Oncogene Proteins c-myc / Q000096:biosynthesis* / Q000235:genetics; D012190:Retroviridae / Q000235:genetics
D000952:Antigens, Polyomavirus Transforming; D016271:Proto-Oncogene Proteins c-myc; D003907:Dexamethasone