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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
13
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pubmed:dateCreated |
1991-6-5
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pubmed:abstractText |
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.
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pubmed:keyword |
http://linkedlifedata.com/resource/pubmed/keyword/ANTIBIOTICS,
http://linkedlifedata.com/resource/pubmed/keyword/Biology,
http://linkedlifedata.com/resource/pubmed/keyword/Breast Cancer,
http://linkedlifedata.com/resource/pubmed/keyword/Cancer,
http://linkedlifedata.com/resource/pubmed/keyword/Clinical Research,
http://linkedlifedata.com/resource/pubmed/keyword/DRUGS,
http://linkedlifedata.com/resource/pubmed/keyword/Developed Countries,
http://linkedlifedata.com/resource/pubmed/keyword/Dexamethasone Acetate,
http://linkedlifedata.com/resource/pubmed/keyword/Diseases,
http://linkedlifedata.com/resource/pubmed/keyword/Endocrine System,
http://linkedlifedata.com/resource/pubmed/keyword/Europe,
http://linkedlifedata.com/resource/pubmed/keyword/France,
http://linkedlifedata.com/resource/pubmed/keyword/Hormone Antagonists,
http://linkedlifedata.com/resource/pubmed/keyword/Hormone Receptors,
http://linkedlifedata.com/resource/pubmed/keyword/Hormones,
http://linkedlifedata.com/resource/pubmed/keyword/In Vitro,
http://linkedlifedata.com/resource/pubmed/keyword/LIPIDS,
http://linkedlifedata.com/resource/pubmed/keyword/Lipid Metabolic Effects,
http://linkedlifedata.com/resource/pubmed/keyword/Mammary Gland Effects,
http://linkedlifedata.com/resource/pubmed/keyword/Mediterranean Countries,
http://linkedlifedata.com/resource/pubmed/keyword/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/keyword/Neoplasms,
http://linkedlifedata.com/resource/pubmed/keyword/Physiology,
http://linkedlifedata.com/resource/pubmed/keyword/Progestational Hormones,
http://linkedlifedata.com/resource/pubmed/keyword/Research Methodology,
http://linkedlifedata.com/resource/pubmed/keyword/Research Report,
http://linkedlifedata.com/resource/pubmed/keyword/Ru-486,
http://linkedlifedata.com/resource/pubmed/keyword/Treatment,
http://linkedlifedata.com/resource/pubmed/keyword/Western Europe
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Dactinomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Deoxyadenosines,
http://linkedlifedata.com/resource/pubmed/chemical/Dexamethasone,
http://linkedlifedata.com/resource/pubmed/chemical/Fatty Acid Synthetase Complex,
http://linkedlifedata.com/resource/pubmed/chemical/Mifepristone,
http://linkedlifedata.com/resource/pubmed/chemical/Progestins,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Progesterone,
http://linkedlifedata.com/resource/pubmed/chemical/cordycepin
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
5
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pubmed:volume |
266
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
8220-4
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pubmed:dateRevised |
2006-11-15
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pubmed:otherAbstract |
PIP: The mechanism of action of RU-486 on the progesterone receptor was examined in MCF7 breast cancer cells in vitro, using messenger RNA (mRNA) for the enzyme fatty acid synthetase (FAS) as an indicator. Transcription and half-life of FAS mRNA were assayed by Northern Blot hybridization, with the progestin R5020 as a reference, and the C3 and actin clones as negative controls. Incubating MCF7 breast cancer cells for 5 or 48 hours with RU-486 decreased FAS gene transcription, and inhibited synthesis of its mRNA 50%. Paradoxically, RU-486 lengthened the half-life of FAS mRNA from 6 to 24 hours, as demonstrated by short-term cell labeling with tritiated uridine in the presence of DNA synthesis inhibitors actinomycin D or cordycepin. This treatment did not stabilize mRNA for C3 or actin. The half-size of FAS mRNA was increased from 6 to 26 hours as measured by a pulse-chase experiment. The steady state level of FAS mRNA doubled in a 2-day incubation. The fact that the glucocorticoid dexamethasone did not stabilize FAS mRNA in MDA-MB23 breast cancer cells suggested that the observed stabilization of mRNA in the RU-486 experiments is mediated by the progesterone receptor. This is the 1st demonstration that a steroid hormone antagonist prevents transcription of a regulated gene, but stabilizes its mRNA, suggesting 2 different regulatory steps.
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pubmed:meshHeading |
pubmed-meshheading:2022639-Cell Line,
pubmed-meshheading:2022639-Dactinomycin,
pubmed-meshheading:2022639-Deoxyadenosines,
pubmed-meshheading:2022639-Dexamethasone,
pubmed-meshheading:2022639-Fatty Acid Synthetase Complex,
pubmed-meshheading:2022639-Gene Expression,
pubmed-meshheading:2022639-Half-Life,
pubmed-meshheading:2022639-Humans,
pubmed-meshheading:2022639-Mifepristone,
pubmed-meshheading:2022639-Progestins,
pubmed-meshheading:2022639-RNA, Messenger,
pubmed-meshheading:2022639-Receptors, Progesterone,
pubmed-meshheading:2022639-Transcription, Genetic,
pubmed-meshheading:2022639-Tumor Cells, Cultured
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pubmed:year |
1991
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pubmed:articleTitle |
The anti-progestin RU486 stabilizes the progestin-induced fatty acid synthetase mRNA but does not stimulate its transcription.
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pubmed:affiliation |
Institut National de la Santé et de la Recherche Médicale U 148, Unit-Hormones and Cancer, Montpellier, France.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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