Dexamethasone decreases urokinase plasminogen activator mRNA stability in MAT 13762 rat mammary carcinoma cells.
The glucocorticoid dexamethasone was observed to decrease urokinase plasminogen activator (uPA) RNA levels from within 1 h of treatment of MAT 13762 mammary adenocarcinoma cells. The drug did not alter the rate of uPA gene transcription in these cells, but decreased the stability of cytoplasmic uPA mRNA transcripts. Results from cycloheximide and actinomycin D experiments indicated that the dexamethasone-mediated reduction in uPA RNA required both new protein and RNA synthesis. Based on these results, we propose that dexamethasone induces a short-lived protein(s) which down-regulates uPA RNA levels post-transcriptionally in these metastatic tumour cells.
Henderson
B R
BR
Department of Medicine, University of Sydney, Westmead Hospital, New South Wales, Australia.
Kefford
R F
RF
D000818:Animals; D003907:Dexamethasone / Q000494:pharmacology*; D004355:Drug Stability; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000201:enzymology* / Q000235:genetics; D011499:Protein Processing, Post-Translational / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured; D014568:Urokinase-Type Plasminogen Activator / Q000235:genetics* / Q000378:metabolism
D012333:RNA, Messenger; D003907:Dexamethasone; D014568:Urokinase-Type Plasminogen Activator