Regulation of the nitric oxide pathway genes by tetrahydrofurandiols: microarray analysis of MCF-7 human breast cancer cells.
THF-diols (9,12-oxy-10,13-dihydroxyoctadecanoic and 10,13-oxy-9,12-dihydroxyoctadecanoic acids) are endocrine disrupters in rats and mitogens in breast cancer cells. Microarray analyses and real-time PCR analyses on RNA from THF-treated MCF-7 cells revealed a number of genes (caveolin 1, heat shock protein 90 alpha and 90 beta, vascular endothelial growth factor, ATPase, Ca++ transporting, ubiquitous) in the nitric oxide pathway (NOP) were targets for THF-diols. Chromatin immunoprecipitation studies suggest THF-diols modify of histone H4 acetylation at the caveolin 1 promoter via an epigenetic mechanism. These findings are consistent with the well-known involvement of NOP genes in cell proliferation and sexual behavior.
Shoulars
Kevin
K
Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Room 405A, Houston, TX 77030, USA.
Rodriguez
Mary Ann
MA
Thompson
Trellis
T
Turk
John
J
Crowley
Jan
J
Markaverich
Barry M
BM
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000235:genetics*; D045744:Cell Line, Tumor; D004591:Electrophoresis, Polyacrylamide Gel; D052244:Endocrine Disruptors / Q000494:pharmacology*; D005260:Female; D005663:Furans / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D047468:Immunoprecipitation; D009569:Nitric Oxide / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics*
D052244:Endocrine Disruptors; D005663:Furans; D009569:Nitric Oxide