Insulin enhances glucocorticoid induction of gene expression in a sequence specific manner.
Glucocorticoid receptor (GR) induces transcriptional activation of specific genes by binding to cis-acting enhancer sequences termed glucocorticoid responsive elements (GREs). Insulin regulates gene transcription part of which is mediated sequences dominated by GREs. By transient expression in HTC cells of fusion gene consist MMTV 5' flanking sequences containing the GREs on the thymidine kinase promoter (TK) and the coding region of the chloramphenicol acetyl transferase gene (CAT), we demonstrate that insulin increases 2-fold the produced induction from dexamethasone, while insulin alone does not exceed any significant effect. This synergistic effect of insulin is sequence specific since, expression of the glucocorticoid unresponsive gene RSV-CAT at the same cell line is affected neither by insulin nor dexamethasone or both. Transient expression of CAT constructs with progressive 5' deletion mutants of mouse mammary tumor virus (MMTV) promoter, fail to detect a cis-acting insulin responsive DNA element, that participates in increased dexamethasone mediated induction. We believe that insulin activates an intracellular mediator-transcription factor, that stimulates gene expression indirectly, by interaction with the glucocorticoid receptor.
Tsawdaroglou
N H
NH
National Hellenic Research Foundation, Biological Research, Athens, Greece.
Georgakopoulos
A
A
Nikodimou
E
E
D000818:Animals; D002460:Cell Line; D002482:Cellulose / Q000031:analogs & derivatives / Q000378:metabolism; D015500:Chloramphenicol O-Acetyltransferase / Q000235:genetics; D004247:DNA / Q000378:metabolism; D003907:Dexamethasone / Q000494:pharmacology*; D004742:Enhancer Elements, Genetic; D015870:Gene Expression / Q000187:drug effects*; D007328:Insulin / Q000494:pharmacology*; D007700:Kinetics; D008324:Mammary Tumor Virus, Mouse / Q000235:genetics; D011401:Promoter Regions, Genetic; D011965:Receptors, Glucocorticoid / Q000378:metabolism*; D013937:Thymidine Kinase / Q000235:genetics; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection
C033190:DNA-cellulose; D007328:Insulin; D011965:Receptors, Glucocorticoid; D003907:Dexamethasone; D002482:Cellulose; D004247:DNA; D015500:Chloramphenicol O-Acetyltransferase; D013937:Thymidine Kinase