| Proteinase inhibitor 9, an inhibitor of granzyme B-mediated apoptosis, is a primary estrogen-inducible gene in human liver cells. | |
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MedLine Citation:
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PMID: 10681578 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Although liver is an estrogen target tissue, the number of hepatic genes known to be directly induced by estrogen is very small. We identified proteinase inhibitor 9, or PI-9, as being rapidly and strongly induced by estrogen in an estrogen receptor-positive human liver cell line (HepG2-ER7). Since PI-9 mRNA was also induced by estrogen in a human liver biopsy sample, PI-9 is a genuine estrogen-regulated human gene. PI-9 is a potent inhibitor of granzyme B and of granzyme B-mediated apoptosis. Estrogens induced PI-9 mRNA within 2 h, PI-9 mRNA levels reached a plateau of 30-40-fold induction in 4 h, and induction was not blocked by cycloheximide, indicating that induction of PI-9 mRNA is a primary response. The antiestrogen trans-hydroxytamoxifen was a partial agonist for PI-9 mRNA induction, whereas the antiestrogen ICI 182, 780 was a pure antagonist. Western blot analysis showed that estrogen strongly increases PI-9 protein levels. Inhibition of transcription with actinomycin D resulted in identical rates of PI-9 mRNA decay in the presence and absence of estrogen. We isolated genomic clones containing the PI-9 promoter region, identified a putative transcription start site, and carried out transient transfections of PI-9-luciferase reporter gene constructs. The estrogen, moxestrol, elicited a robust induction from the PI-9-luciferase reporter. Mutational inactivation of three potential imperfect estrogen response elements in the PI-9 5'-flanking region had no effect on moxestrol estrogen receptor induction. |
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Authors:
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H Kanamori; S Krieg; C Mao; V A Di Pippo; S Wang; D A Zajchowski; D J Shapiro |
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Publication Detail:
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Type: Journal Article; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S. |
Journal Detail:
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Title: The Journal of biological chemistry Volume: 275 ISSN: 0021-9258 ISO Abbreviation: J. Biol. Chem. Publication Date: 2000 Feb |
Date Detail:
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Created Date: 2000-03-30 Completed Date: 2000-03-30 Revised Date: 2008-11-21 |
Medline Journal Info:
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Nlm Unique ID: 2985121R Medline TA: J Biol Chem Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: 5867-73 Citation Subset: IM |
Affiliation:
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Department of Biochemistry, University of Illinois, Urbana, Illinois 61801, USA. |
| Data Bank Information | |
Bank Name/Acc. No.:
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GENBANK/AF200209 |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects* Base Sequence Blotting, Northern Carcinoma, Hepatocellular / metabolism Dose-Response Relationship, Drug Estrogen Antagonists / pharmacology Estrogens / pharmacology* Ethinyl Estradiol / analogs & derivatives, pharmacology Gene Expression Regulation Granzymes Humans Liver / metabolism Molecular Sequence Data Promoter Regions, Genetic RNA, Messenger / drug effects Response Elements Reverse Transcriptase Polymerase Chain Reaction Serine Endopeptidases / metabolism* Serine Proteinase Inhibitors / genetics, physiology Serpins / genetics, physiology* Time Factors Transcription, Genetic / drug effects Tumor Cells, Cultured |
| Grant Support | |
ID/Acronym/Agency:
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HD-16720/HD/NICHD NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Estrogen Antagonists; 0/Estrogens; 0/RNA, Messenger; 0/SERPINB9 protein, human; 0/Serine Proteinase Inhibitors; 0/Serpins; 34816-55-2/moxestrol; 57-63-6/Ethinyl Estradiol; EC 3.4.21.-/GZMB protein, human; EC 3.4.21.-/Granzymes; EC 3.4.21.-/Serine Endopeptidases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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