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| Status |
Public on Feb 26, 2008 |
| Title |
Farnesol-induced apoptosis in human lung carcinoma cells is coupled to the endoplasmic reticulum (ER) stress response |
| Platform organism |
Homo sapiens |
| Sample organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Farnesol (FOH) and other isoprenoid alcohols induce apoptosis in various carcinoma cells and inhibit tumorigenesis in several in vivo models. However, the mechanisms by which these isoprenoids mediate their effects are not yet fully understood. In this study, we show that FOH is effective inducer of apoptosis in several lung carcinoma cells, including H460 cells. This induction is associated with activation of caspase-3, -9, and -12, and cleavage of PARP. To obtain insight into the mechanism involved in FOH-induced apoptosis, we compared the gene expression profiles of FOH-treated and control H460 cells using microarray analysis. This analysis revealed that many of the genes implicated in endoplasmic reticulum (ER) stress, including ATF3, CHOP/GADD153, HERPUD1, BIP (GRP78), XBP1, PDIA4, and TDAG51, were highly up-regulated within 4 hr of FOH treatment suggesting that FOH-induced apoptosis involves an ER-stress response. This was supported by observations showing that treatment with FOH induces phosphorylation of eIF2alpha. FOH induces activation of several MAPK pathways, including p38, MEK-ERK, and JNK. Inhibition of MEK1/2 by U0126 inhibited the induction of ER stress-response genes. In addition, knockdown of the MEK1/2 and JNK1/2 expression by short interfering RNA (siRNA) effectively inhibited the induction of apoptosis and activation of caspase-3 and cleavage of PARP by FOH. However, only MEK1/2 siRNAs reduced the expression of ER stress-related genes and inhibited phosphorylation of eIF2alpha. Our results demonstrate that FOH-induced apoptosis is coupled to ER stress and that activation of MEK1/2 is an upstream event in the FOH-induced ER stress signaling cascade.
Vehicle vs. 4h FOH Signature Gene lists (Replicates 1 & 2) are linked as supplementary files to the Series record.
Keywords: gene expression
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| Overall design |
H460 cells were treated for 4 hours with 250 micromolar FOH or vehicle (DMSO) in duplicate experiments. Each FOH treated sample was compared to its matched Vehicle and dye-flips were performed, resulting in 4 arrays (2 replicate sets x 2 technical replicates).
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| Contributor(s) |
Joo J, Liao G, Collins JB, Grissom SF, Jetten AM |
| Citation(s) |
17699800, 18424438 |
| Submission date |
Mar 06, 2007 |
| Last update date |
Dec 06, 2012 |
| Contact name |
NIEHS Microarray Core |
| E-mail(s) |
microarray@niehs.nih.gov, liuliw@niehs.nih.gov
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| Organization name |
NIEHS
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| Department |
DIR
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| Lab |
Microarray Core
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| Street address |
111 T.W. Alexander Drive
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| City |
RTP |
| State/province |
NC |
| ZIP/Postal code |
27709 |
| Country |
USA |
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| Platforms (1) |
| GPL1708 |
Agilent-012391 Whole Human Genome Oligo Microarray G4112A (Feature Number version) |
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| Samples (4)
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| GSM173160 |
OH1ST vs. 4H1ST Cy3: OH1ST Cy5: 4H1ST |
| GSM173161 |
OH1ST vs. 4H1ST Cy3: 4H1ST Cy5: OH1ST |
| GSM173162 |
OH2ST vs. 4H2ST Cy3: OH2ST Cy5: 4H2ST |
| GSM173163 |
OH2ST vs. 4H2ST Cy3: 4H2ST Cy5: OH2ST |
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| Relations |
| BioProject |
PRJNA98299 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE7215_RAW.tar |
154.4 Mb |
(http)(custom) |
TAR (of TIFF, TXT) |
| GSE7215_Vehicle_vs_4hFOH_1.txt |
978.7 Kb |
(ftp)(http) |
TXT |
| GSE7215_Vehicle_vs_4hFOH_2.txt |
978.7 Kb |
(ftp)(http) |
TXT |
| Processed data included within Sample table |
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