Document Detail


Uterine leiomyomas express a molecular pattern that lowers retinoic acid exposure.
MedLine Citation:
PMID:  17276435     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
William H Catherino; Minnie Malik
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2007-02-02
Journal Detail:
Title:  Fertility and sterility     Volume:  87     ISSN:  1556-5653     ISO Abbreviation:  Fertil. Steril.     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-06-04     Completed Date:  2007-09-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0372772     Medline TA:  Fertil Steril     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1388-98     Citation Subset:  IM    
Affiliation:
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:
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:
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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