Title: Transcription profiling of human prostate cancer cells treated with arachidonic acid reveals induction of 11 genes that are regulated by NFkappaB
Organism(s): Homo sapiens
Description: 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, phosphatidylinositol 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.
Design(s): time_series_design, compound_treatment_design, co-expression_design, transcription profiling by array
Experimental factor(s):
2 recorded
control arachidonic acid
Publication(s): Millie Hughes-Fulford, Chai-Fei Li, Jim Boonyaratanakornkit, Sina Sayyah
Arachidonic acid activates phosphatidylinositol 3-kinase signaling and induces gene expression in prostate cancer. PubMed:16452198

Sample attribute(s):
1 recorded
PC3 cell
Material Type
2 recorded
synthetic_RNA total_RNA
1 recorded
prostate cancer
1 recorded
1 recorded
Homo sapiens
Contact(s): Jim Boonyaratanakornkit
Release Date: 7/3/2007
Submission Date:
Metadata Downloads Download Study Metadata as ISAtabDownload Study Metadata as ISAtab
Assay Downloads
transcription profiling using DNA microarray
8 assays