Document Detail

4-HPR modulates gene expression in ovarian cells.
MedLine Citation:
PMID:  16570282     Owner:  NLM     Status:  MEDLINE    
Ovarian cancer has a high rate of recurrence and subsequent mortality following chemotherapy despite intense efforts to improve treatment outcomes. Recent trials have suggested that retinoids, especially 4-(N-hydroxyphenyl) retinamide (4-HPR), play an important role as a chemopreventive agent and are currently being used in clinical trials for ovarian cancer chemoprevention as well as treatment. This study examines the mechanism of its activity in premalignant and cancer cells. We investigated the modulation of gene expression by 4-HPR in immortalized ovarian surface epithelial (IOSE) cells and ovarian cancer (OVCA433) cells with DNA microarray. Real time RT-PCR and western blotting were used to confirm the microarray results and metabolic changes were examined with optical fluorescence spectroscopy. 4-HPR resulted in an up-regulation of expression of proapoptotic genes and mitochondrial uncoupling protein in OVCA433 cells and modulation of the RXR receptors in IOSE cells, and down-regulation of mutant BRCA genes in both IOSE and OVCA433 cells. 4-HPR had a larger effect on the redox in the 433 cells compared to IOSE. These findings suggest that 4-HPR acts through different mechanisms in premalignant ovarian surface cells and cancer cells, with a preventive effect in premalignant cells and a treatment effect in cancer cells.
Molly Brewer; Nathaniel D Kirkpatrick; J Taylor Wharton; Jian Wang; Kenneth Hatch; Nelly Auersperg; Urs Utzinger; David Gershenson; Robert Bast; Changping Zou
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, Non-P.H.S.    
Journal Detail:
Title:  International journal of cancer. Journal international du cancer     Volume:  119     ISSN:  0020-7136     ISO Abbreviation:  Int. J. Cancer     Publication Date:  2006 Sep 
Date Detail:
Created Date:  2006-06-12     Completed Date:  2006-08-22     Revised Date:  2007-07-24    
Medline Journal Info:
Nlm Unique ID:  0042124     Medline TA:  Int J Cancer     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1005-13     Citation Subset:  IM    
Copyright Information:
Copyright 2006 Wiley-Liss, Inc.
Department of Obstetrics and Gynecology, Division of Gynecologic Oncology, Arizona Cancer Center, Tucson, 85724, USA.
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MeSH Terms
Anticarcinogenic Agents / pharmacology*
Antineoplastic Agents / pharmacology*
Apoptosis / drug effects,  genetics
Blotting, Western
Carrier Proteins / drug effects
Cell Cycle
Cell Line, Tumor
Down-Regulation / drug effects
Fenretinide / pharmacology*
Gene Expression Regulation, Neoplastic / drug effects*
Genes, BRCA1 / drug effects
Genes, BRCA2 / drug effects
Ion Channels
Membrane Proteins / drug effects
Mitochondrial Proteins
Oligonucleotide Array Sequence Analysis
Ovarian Neoplasms / drug therapy,  metabolism*,  prevention & control
Retinoid X Receptors / drug effects
Reverse Transcriptase Polymerase Chain Reaction
Spectrometry, Fluorescence
Up-Regulation / drug effects
Reg. No./Substance:
0/Anticarcinogenic Agents; 0/Antineoplastic Agents; 0/Carrier Proteins; 0/Ion Channels; 0/Membrane Proteins; 0/Mitochondrial Proteins; 0/Retinoid X Receptors; 0/mitochondrial uncoupling protein; 65646-68-6/Fenretinide

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