| An analysis of tamoxifen-stimulated human carcinomas for mutations in the AF-2 region of the estrogen receptor. | |
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MedLine Citation:
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PMID: 8918973 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The estrogen receptor (ER) contains two transcriptional activation domains: AF-1 and AF-2. AF-2 is dependent on a highly species-conserved region of the ER. It has been shown that site-directed point mutations of conserved hydrophobic amino acids within this region reduce estrogen-dependent transcriptional activation. In addition, when these mutated ERs are transfected into HeLa cells, both tamoxifen and ICI 164,384 become strong agonists. The implication is that mutations in this region could account for the tamoxifen-stimulated tumors seen clinically. We performed single stranded conformational polymorphism (SSCP) analysis spanning the entire ER along with DNA sequencing of the AF-2 region of the ER isolated from two different tamoxifen-stimulated breast cancers, MCF-7/TAM and MCF-7/MT2, and a tamoxifen-stimulated endometrial cancer, EnCa 101. In addition, a tamoxifen-stimulated endometrial carcinoma cell line, the Ishikawa cell line, was also studied. There were no mutations found by SSCP analysis and sequencing of all four AF-2 regions also revealed no mutations. Mutations within the AF-2 region of the human ER do not appear to account for the growth of human breast and endometrial carcinomas that are used as reproducible laboratory models of tamoxifen-stimulated growth observed clinically. |
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Authors:
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M M Bilimoria; V J Assikis; H D Muenzner; D M Wolf; P G Satyaswaroop; V C Jordan |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: The Journal of steroid biochemistry and molecular biology Volume: 58 ISSN: 0960-0760 ISO Abbreviation: J. Steroid Biochem. Mol. Biol. Publication Date: 1996 Aug |
Date Detail:
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Created Date: 1997-01-02 Completed Date: 1997-01-02 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 9015483 Medline TA: J Steroid Biochem Mol Biol Country: ENGLAND |
Other Details:
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Languages: eng Pagination: 479-88 Citation Subset: IM |
Affiliation:
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Department of Surgery, Northwestern University Medical School, Chicago, IL 60611, U.S.A. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Carcinoma
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genetics*,
metabolism Endometrial Neoplasms / genetics*, metabolism Estrogen Antagonists / administration & dosage* Female Humans Mutation / drug effects Neoplasms, Experimental / genetics, metabolism Ovarian Neoplasms / genetics*, metabolism Receptors, Estrogen / antagonists & inhibitors, genetics* Sequence Analysis, DNA Tamoxifen / administration & dosage* |
| Chemical | |
Reg. No./Substance:
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0/Estrogen Antagonists; 0/Receptors, Estrogen; 10540-29-1/Tamoxifen |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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