Back to Search
Start Over
Rac1b enhances cell survival through activation of the JNK2/c-JUN/Cyclin-D1 and AKT2/MCL1 pathways
- Source :
- Oncotarget
- Publication Year :
- 2015
-
Abstract
- Rac1b is a constitutively activated, alternatively spliced form of the small GTPase Rac1. Previous studies showed that Rac1b promotes cell proliferation and inhibits apoptosis. In the present study, we used microarray analysis to detect genes differentially expressed in HEK293T cells and SW480 human colon cancer cells stably overexpressing Rac1b. We found that the pro-proliferation genes JNK2, c-JUN and cyclin-D1 as well as anti-apoptotic AKT2 and MCL1 were all upregulated in both lines. Rac1b promoted cell proliferation and inhibited apoptosis by activating the JNK2/c-JUN/cyclin-D1 and AKT2/MCL1 pathways, respectively. Very low Rac1b levels were detected in the colonic epithelium of wild-type Sprague-Dawley rats. Knockout of the rat Rac1 gene exon-3b or knockdown of endogenous Rac1b in HT29 human colon cancer cells downregulated only the AKT2/MCL1 pathway. Our study revealed that very low levels of endogenous Rac1b inhibit apoptosis, while Rac1b upregulation both promotes cell proliferation and inhibits apoptosis. It is likely the AKT2/MCL1 pathway is more sensitive to Rac1b regulation.
- Subjects :
- 0301 basic medicine
rac1 GTP-Binding Protein
Rac1b
Cell Survival
RAC1
Rats, Sprague-Dawley
03 medical and health sciences
Cyclin D1
Downregulation and upregulation
Cell Line, Tumor
Medicine
Animals
Humans
Mitogen-Activated Protein Kinase 9
JNK2
AKT2
business.industry
Cell growth
HEK 293 cells
c-jun
apoptosis
Microarray Analysis
3. Good health
Cell biology
Rats
030104 developmental biology
HEK293 Cells
cell proliferation
Oncology
Apoptosis
Myeloid Cell Leukemia Sequence 1 Protein
Signal transduction
business
Proto-Oncogene Proteins c-akt
Signal Transduction
Research Paper
Subjects
Details
- ISSN :
- 19492553
- Volume :
- 7
- Issue :
- 14
- Database :
- OpenAIRE
- Journal :
- Oncotarget
- Accession number :
- edsair.doi.dedup.....2059c70b635fcaf8809adcfc37ed5d0f