Abstract
Progestins induce fatty acid synthetase (FAS) in breast cancer cell lines, both increasing its gene transcription and mRNA stabilization (Joyeux, C., Rochefort, H., and Chalbos, D. (1989) Mol. Endocrinol. 4, 681-686). In vitro run-on transcription assays show that RU486, in contrast to progestin, inhibits FAS transcription by 40-50%. Moreover and surprisingly, anti-progestin RU486 also stabilizes FAS mRNA 3- to 4-fold in MCF7 cells as measured by chase experiments in the presence of actinomycin D or cordycepin or after short cell labeling with [3H]uridine. Dexamethasone is inefficient in increasing the half-life of FAS mRNA in MCF7 cells. RU486 had no effect on MDA-MB 231 cells which contain glucocorticoid but no progesterone receptors, indicating that the progesterone receptor is implicated in this regulation. RU486-induced mRNA stabilization allows delayed accumulation of FAS mRNA. These results indicate that the progesterone receptor can be activated separately to stimulate gene transcription or stabilize mRNA.
Highlights
Progestins induce fatty acid synthetase (FAS) in breast cancer cell lines, both increasing its genetranscription and mRNA stabilization (Joyeux, C., Rochefort, H., andChalbos, D. (1989) Mol
In order to determine whether thiesraeny parallelbetween the efficiency of an antihormone to stimulate transcription and to stabilize mRNA, we studied RU486 regulation of the progestin-induced gene coding for fatty acid synthetase (18), which in breast cancercells is regulatedby progestin both at thetranscriptionandmRNAstabilization levels (19)
We show here thatRU486 when added alonedecreases FAS gene transcription,but stabilizes FASmRNA,as progesterone does
Summary
Progestins induce fatty acid synthetase (FAS) in breast cancer cell lines, both increasing its genetranscription and mRNA stabilization (Joyeux, C., Rochefort, H., andChalbos, D. (1989) Mol. RU486 Increases FAS mRNA Stability-In a first series of experiments, thehalf-life of FAS mRNA was estimated after treatment of MCF7 cells with gene transcription inhibitors (Fig. 2).
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