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| Status |
Public on Dec 12, 2007 |
| Title |
Gene Expression in S49 Deathless (D-) cell variant |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
The second messenger cAMP acts via protein kinase A (PKA) to induce apoptosis by mechanisms that are poorly understood. Here, we assessed a role for mitochondria and analyzed gene expression in cAMP/PKA-promoted apoptosis by comparing wild-type (WT) S49 lymphoma cells and the S49 variant, D- (cAMP-deathless), which lacks cAMP-promoted apoptosis but has wild-type levels of PKA activity and cAMP-promoted G1 growth arrest. Treatment of WT, but not D-, S49 cells with 8-CPT-cAMP for 24 h induced loss of mitochondrial membrane potential, mitochondrial release of cytochrome c and Smac and increase in caspase-3 activity. Gene expression analysis (using Affymetrix 430 2.0 Arrays) revealed that WT and D- cells incubated with 8-CPT-cAMP have similar, but non-identical, extents of cAMP-regulated gene expression at 2h (~800 transcripts) and 6h (~1000 transcripts) (|Fold|>2, P<0.06); by contrast, at 24h ~2500 and ~1100 transcripts were changed in WT and D- cells, respectively. Using an approach that combined regression analysis, clustering and functional annotation to identify transcripts that showed differential expression between WT and D- cells, we found differences in cAMP-mediated regulation of mRNAs involved in transcriptional repression, apoptosis, the cell cycle, RNA splicing, Golgi and lysosomes. The 2 cell lines differed in CREB phosphorylation and expression of the transcriptional inhibitor Icer and in cAMP-regulated expression of genes in the Inhibitor of apoptosis (IAP) and Bcl families. The findings indicate that cAMP/PKA-promoted apoptosis of lymphoid cells occurs via mitochondrial-mediated events and imply that such apoptosis involves gene networks in multiple biochemical pathways.
Keywords: time course
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| Overall design |
S49 D- cells were treated with 8-CPT-cAMP over the course of 24 hours. Cells were prepared for hybridization to microarrays at times 0-untreated, 2h, 6h, and 24h after treatment with 8-CPT-cAMP. Experimental replicates were as follows n=4 for time 0 and n=3 for 2, 6, and 24h post treatment.
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| Contributor(s) |
Zambon AC, Zhang L, Insel PA |
| Citation(s) |
18048352 |
| Submission date |
Nov 29, 2007 |
| Last update date |
Jan 08, 2019 |
| Contact name |
Alexander C Zambon |
| Organization name |
Keck Graduate Institute
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| Department |
Biopharmaceutical Sciences
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| Lab |
Zambon
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| Street address |
517 Watson Drive
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| City |
Claremont |
| State/province |
CA |
| ZIP/Postal code |
91711 |
| Country |
USA |
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| Platforms (1) |
| GPL339 |
[MOE430A] Affymetrix Mouse Expression 430A Array |
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| Samples (26)
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| GSM245893 |
D- S49_untreated_time0, biological rep1 |
| GSM245894 |
D- S49_untreated_time0, biological rep2 |
| GSM245895 |
D- S49_untreated_time0, biological rep3 |
| GSM245896 |
D- S49_untreated_time0, biological rep4 |
| GSM245897 |
D- S49_treated_2h, biological rep1 |
| GSM245898 |
D- S49_treated_2h, biological rep2 |
| GSM245899 |
D- S49_treated_2h, biological rep3 |
| GSM245900 |
D- S49_treated_6h, biological rep1 |
| GSM245901 |
D- S49_treated_6h, biological rep2 |
| GSM245902 |
D- S49_treated_6h, biological rep3 |
| GSM245903 |
D- S49_treated_24h, biological rep1 |
| GSM245904 |
D- S49_treated_24h, biological rep2 |
| GSM245905 |
D- S49_treated_24h, biological rep3 |
| GSM248218 |
WT S49_untreated_time0, biological rep1 |
| GSM248219 |
WT S49_untreated_time0, biological rep2 |
| GSM248220 |
WT S49_untreated_time0, biological rep3 |
| GSM248221 |
WT S49_untreated_time0, biological rep4 |
| GSM248222 |
WT S49_untreated_2h, biological rep1 |
| GSM248223 |
WT S49_untreated_2h, biological rep2 |
| GSM248224 |
WT S49_untreated_2h, biological rep3 |
| GSM248225 |
WT S49_untreated_6h, biological rep1 |
| GSM248226 |
WT S49_untreated_6h, biological rep2 |
| GSM248227 |
WT S49_untreated_6h, biological rep3 |
| GSM248228 |
WT S49_untreated_24h, biological rep1 |
| GSM248229 |
WT S49_untreated_24h, biological rep2 |
| GSM248230 |
WT S49_untreated_24h, biological rep3 |
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| Relations |
| BioProject |
PRJNA103643 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE9727_RAW.tar |
90.7 Mb |
(http)(custom) |
TAR (of CEL) |
| Processed data included within Sample table |
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