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Series GSE3737 Query DataSets for GSE3737
Status Public on Jan 01, 2006
Title Omega-6 fatty acids, arachidonic acid (AA) activates PI3K signaling and induces gene expression in prostate cancer
Organism Homo sapiens
Experiment type Expression profiling by array
Summary Essential fatty acids (FA) are not only energy-rich molecules; they are also an important component of the membrane bilayer and recently have been implicated in induction of fatty acid synthase (FAS) and other genes. Using gene chip analysis, we have found that arachidonic acid (AA), an omega-6 fatty acid, induced 11 genes that are regulated by NFkappaB. We verified gene induction by omega-6 fatty acids including COX2, IKBA, NFKB, GMCSF, IL1B, CXCL1, TNFA, IL6, LTA, IL8, PPARG, and ICAM1 using qRTPCR. PGE2 synthesis was increased within 5min of addition of AA. Analysis of upstream signal transduction showed that within 5min of FA addition, phophatidylinositol 3-kinase (PI3K) was significantly activated followed by activation of Akt at 30min. ERK1 and 2, p38, and SAPK/JNK were not phosphorylated after omega-6 FA addition. Thirty minutes after FA addition, we found a significant 3-fold increase in translocation of NFkappaB transcription factor to the nucleus. Addition of non-steroidal anti-inflammatory drug (NSAID) caused a decrease in cox-2 protein synthesis, PGE2 synthesis as well as inhibition of PI3K activation. We have previously shown that AA induced proliferation is also blocked (P<0.001) by PI3K inhibitor LY294002. LY294002 also significantly inhibited the AA induced gene expression of COX2, IL1B, GMCSF, and ICAM1. Taken together, the data suggests that AA via conversion to PGE2 plays an important role in stimulation of growth related genes and proliferation via PI3K signaling and NFkappaB translocation to the nucleus.
Keywords: Time course of Prostate Cancer Activation by Arachidonic Acid
Overall design PC-3 prostate cancer cells were incubated with 5 µg/mL AA in RPMI containing 0.25 mg/mL albumin for 2hr. Control cells were treated with albumin alone and remained unactivated. Total RNA was isolated and relative gene expression was analyzed by Affymetrix gene arrays and then verified by qRTPCR. Microarrays for untreated and treated samples were done in quadruplicates.
Contributor(s) Hughes-Fulford M, Li C, Boonyaratanakornkit JB, Sayyah S
Citation(s) 16452198
Submission date Dec 02, 2005
Last update date Aug 10, 2018
Contact name Jim Boonyaratanakornkit
Phone 301-594-2589
Organization name NIH - NIAID
Department LID
Street address 50 South Dr, Bldg 50, Rm 6513
City Bethesda
State/province MD
ZIP/Postal code 20892
Country USA
Platforms (1)
GPL96 [HG-U133A] Affymetrix Human Genome U133A Array
Samples (8)
GSM86079 1 PC3 0hr
GSM86080 1 PC3 0hra
GSM86081 2 PC3 0hr
Affiliated with GSE67157
BioProject PRJNA93899

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Supplementary file Size Download File type/resource
GSE3737_RAW.tar 26.1 Mb (http)(custom) TAR (of CEL, EXP)
Raw data provided as supplementary file

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