| Uterine leiomyomas express a molecular pattern that lowers retinoic acid exposure. | |
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MedLine Citation:
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PMID: 17276435 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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OBJECTIVE: To analyze expression of the retinoic acid signaling pathway genes that are involved in retinol metabolism, transport, transcriptional activation, and transcriptional products in spontaneous human leiomyomas. DESIGN: Laboratory study of human leiomyoma and patient-matched myometrial tissue. PATIENT(S): Eight women undergoing hysterectomy for symptomatic leiomyomas. INTERVENTION(S): Confirmation of an altered retinoic acid pathway analyzed by microarray, real time reverse transcription-polymerase chain reaction, Western blot, immunohistochemistry, and high-performance liquid chromatography (HPLC). MAIN OUTCOME MEASURE(S): Gene and protein expression. RESULT(S): Regardless of patient demographics and leiomyoma location and size, we found decreased expression of the major genes involved in retinoic acid pathway including alcohol dehydrogenase-1 (-3.97- +/- 0.03-fold), aldehyde dehydrogenase-1 (-3.1- +/- 0.07-fold), cellular retinol binding protein-1 (-2.62- +/- 0.04-fold), and cellular retinoic acid binding protein-1 (-2.42- +/- 0.20-fold). Cytochrome P450 (CYP 26A1), which is responsible for retinoic acid metabolism, was highly up-regulated in leiomyomas (+5.4- +/- 0.53-fold). Nuclear receptors demonstrated a complex pattern of under-expression (RARalpha, RARbeta, RXRalpha, RXRgamma) and over-expression (RARgamma, RXRbeta) at both the mRNA and protein level. Differences in protein amounts were confirmed by Western blot. Finally, a reduced amount of cellular ATRA and 9-cis retinoic acid was confirmed by HPLC in leiomyomas compared with myometrial tissues. CONCLUSION(S): Molecular alterations in the retinoic acid pathway of leiomyomata result in a decrease in retinoic acid exposure. |
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Authors:
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William H Catherino; Minnie Malik |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't Date: 2007-02-02 |
Journal Detail:
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Title: Fertility and sterility Volume: 87 ISSN: 1556-5653 ISO Abbreviation: Fertil. Steril. Publication Date: 2007 Jun |
Date Detail:
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Created Date: 2007-06-04 Completed Date: 2007-09-14 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372772 Medline TA: Fertil Steril Country: United States |
Other Details:
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Languages: eng Pagination: 1388-98 Citation Subset: IM |
Affiliation:
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Department of Obstetrics and Gynecology, Uniformed Services University of the Health Sciences, Bethesda, Maryland 20814-4712, USA. catheriw@mail.nih.gov |
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Female Gene Expression Regulation, Neoplastic* Humans Hysterectomy Immunohistochemistry Leiomyoma / genetics* Menstrual Cycle Middle Aged Myometrium / physiology Neoplasm Proteins / genetics, isolation & purification Oligonucleotide Array Sequence Analysis RNA, Neoplasm / genetics, isolation & purification Reverse Transcriptase Polymerase Chain Reaction Tretinoin / metabolism* Uterine Neoplasms / genetics*, surgery |
| Chemical | |
Reg. No./Substance:
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0/Neoplasm Proteins; 0/RNA, Neoplasm; 302-79-4/Tretinoin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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