Unknown,Transcriptomics,Genomics,Proteomics

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Transcription profiling of human prostate cancer cells with arachidonic acid reveals induction of 11 genes that are regulated by NFkappaB

ABSTRACT: 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.

ORGANISM(S): Homo sapiens

SUBMITTER: Jim Boonyaratanakornkit

PROVIDER: E-GEOD-3737 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Arachidonic acid activates phosphatidylinositol 3-kinase signaling and induces gene expression in prostate cancer.

Hughes-Fulford Millie M Li Chai-Fei CF Boonyaratanakornkit Jim J Sayyah Sina S

Cancer research 20060201 3

Essential fatty acids 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 and other genes. Using gene chip analysis, we have found that arachidonic acid, an omega-6 fatty acid, induced 11 genes that are regulated by nuclear factor-kappaB (NF-kappaB). We verified gene induction by omega-6 fatty acid, including COX-2, IkappaBalpha, NF-kappaB, GM-CSF, IL-1beta, CXCL-1, TNF-alpha, IL-6, ...[more]

PMID: 16452198

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Project description:The optimal ratio of omega-6 to omega-3 polyunsaturated fatty acids (PUFAs) is important for keeping homeostasis of biological processes and metabolism, yet the underlying biological mechanism is poorly understood. The objective of this study was to identify changes in the pig liver transcriptome induced by a diet enriched with omega-6 and omega-3 fatty acids, and to characterize the biological mechanisms related to PUFA metabolism. Polish Landrace pigs (n =12) were fed diet enriched with linoleic acid (LA, omega-6) and alpha-linolenic acid (ALA, omega-3 family) or standard diet as a control. The fatty acids profiling was assayed in order to verify how feeding influenced the fatty acids content in liver, and subsequently next-generation sequencing (NGS) was used to identify differentially expressed genes (DEG) between transcriptomes between dietary groups. The biological mechanisms and pathway interaction networks were identified by analysis in DAVID and Cytoscape tools. Fatty acids profile analysis indicated a higher contribution of PUFAs in liver for LA and ALA-enriched diet group, particularly for the omega-3 fatty acids family, but not omega-6. Next-generation sequencing identified 3,565 DEG, 1,484 of which were induced and 2,081 were suppressed by PUFA supplemenation. Low ratio of omega-6/-3 fatty acids resulted in modulation of fatty acids metabolism pathways and over-representation of genes involved in membrane composition, signal transduction and immune response pathways. In conclusion, a diet enriched with omega-6 and omega-3 fatty acids altered the transcriptomic profile of the pig liver and affected a set of genes involved in metabolic pathways important to animal health status. Hepatic mRNA profiles of Polish Landrace pig breed fed two different diets, were generated by deep sequencing, using Illumina MiSeq. Experimental diet was enriched with polyunsaturated fatty acids (omega-6 and omega-3), while standard diet remain as a cotrol. 2 pooled samples each containing RNA extracts from 6 individuals livers were analyzed.

Dataset Information

Transcription profiling of human prostate cancer cells with arachidonic acid reveals induction of 11 genes that are regulated by NFkappaB

Publications

Arachidonic acid activates phosphatidylinositol 3-kinase signaling and induces gene expression in prostate cancer.

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