Document Detail

Negative regulation of glucocorticoid-dependent induction of c-fos by ras in intestinal epithelial cells.
MedLine Citation:
PMID:  10395074     Owner:  NLM     Status:  MEDLINE    
In order to investigate the regulatory mechanisms involved in the expression of fos and jun family members by glucocorticoids, and the effect of ras transformation in intestinal epithelial cells, we used the rat cell line IEC-6. Dexamethasone treatment induced transiently c-jun mRNAs, in contrast to the sustained expression of c-fos, whereas its effect on junB expression resulted in a later increase. Dexamethasone-dependent stimulation of c-fos and c-jun was modulated predominantly at the level of transcription. Sustained levels of induced c-fos and c-jun proteins were observed after dexamethasone treatment. AP-1 DNA-binding capacity of c-fos, and to a smaller extent c-jun, was increased by glucocorticoids later than after serum treatment. To analyse the effect of ras on the glucocorticoid response of AP-1 components, we studied several IEC-6 cell clones transformed by the Ha-ras oncogene. In comparison to normal cells, these transformants displayed increased AP-1 DNA-binding activity with higher levels of junB and variable levels of c-jun in the AP-1 complex. Ras transformation repressed the growth-inhibitory properties of glucocorticoids. Furthermore, ras inhibited the glucocorticoid-dependent induction of c-fos protein and mRNA, leading to changes in AP-1 composition as compared to normal cells. As assessed by transient transfection luciferase assays, glucocorticoids induced significantly a minimal promoter containing 3 copies of an AP-1 DNA-binding site as well as the murine c-fos -276 to +112 promoter in non-transformed cells. In contrast, glucocorticoid addition did not induce these constructs in two ras transformed cell lines. These results suggest that ras negatively modulates specific responses of intestinal epithelial cells to glucocorticoids.
F Boudreau; S Zannoni; N Pelletier; T Bardati; S J Yu; C Asselin
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Molecular and cellular biochemistry     Volume:  195     ISSN:  0300-8177     ISO Abbreviation:  Mol. Cell. Biochem.     Publication Date:  1999 May 
Date Detail:
Created Date:  1999-10-28     Completed Date:  1999-10-28     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0364456     Medline TA:  Mol Cell Biochem     Country:  NETHERLANDS    
Other Details:
Languages:  eng     Pagination:  99-111     Citation Subset:  IM    
Département d'Anatomie et Biologie Cellulaire, Faculté de Médecine, Université de Sherbrooke, Québec, Canada.
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MeSH Terms
Blotting, Northern
Blotting, Western
Cell Fractionation
Cell Line
Cell Transformation, Neoplastic / genetics
Epithelial Cells / drug effects,  metabolism*
Gene Expression Regulation / drug effects*
Glucocorticoids / antagonists & inhibitors,  pharmacology*
Intestinal Mucosa / cytology,  drug effects,  metabolism*
Macromolecular Substances
Nuclear Proteins / analysis
Proto-Oncogene Proteins c-fos / biosynthesis*,  genetics
Proto-Oncogene Proteins p21(ras) / genetics,  physiology*
RNA, Messenger / analysis
Transcription Factor AP-1 / chemistry,  metabolism
Reg. No./Substance:
0/Glucocorticoids; 0/Macromolecular Substances; 0/Nuclear Proteins; 0/Proto-Oncogene Proteins c-fos; 0/RNA, Messenger; 0/Transcription Factor AP-1; EC Proteins p21(ras)

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