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Differential gene expression profiles of Jnk1- and Jnk2-deficient murine fibroblast cells
Nanyue Chen1, Qing-Bai She, Ann M Bode
1The Hormel Institute, University of Minnesota, Austin, Minnesota 55912.
Abstract:
c-Jun NH(2)-terminal kinase (JNK) 1 and JNK2 have been assumed to complement each other and mediate the same or similar biological functions. However, our recent reports indicated that 7,12-dimethylbenz(a)anthracene/12-O-tetradecanoylphorbol-13-acetate-induced tumor development is suppressed in Jnk2 knockout mice but enhanced in Jnk1 knockout mice. In the present work, primary embryo cells were isolated from wild-type, Jnk1(-/-) and Jnk2(-/-) mice and used for cDNA microarray analysis. The patterns of gene expression in Jnk1(-/-), Jnk2(-/-), and wild-type cells are different. After 12-O-tetradecanoylphorbol-13-acetate treatment, the changes in the gene expression profiles in three different kinds of cells appear to agree with the differences in susceptibility to tumorigenesis of each respective animal model. These results suggest that JNK1 and JNK2 proteins have different roles in modulating cell function.
Insights
c-Jun NH(2)-terminal kinase (JNK) 1 and JNK2 proteins have distinct roles in cell function and tumor development. Gene expression analysis reveals unique patterns, challenging the assumption of JNK1 and JNK2 functional redundancy.
Area of Science:
- Molecular Biology
- Cell Signaling
- Cancer Research
Background:
- c-Jun NH(2)-terminal kinase (JNK) 1 and JNK2 are believed to have complementary functions.
- Previous studies showed opposing effects of JNK1 and JNK2 knockout on chemical-induced tumor development.
Purpose of the Study:
- To investigate the distinct roles of JNK1 and JNK2 in cellular function and gene expression.
- To analyze differences in gene expression patterns between wild-type, Jnk1(-/-), and Jnk2(-/-) cells.
Main Methods:
- Primary embryo cells were isolated from wild-type, Jnk1 knockout, and Jnk2 knockout mice.
- cDNA microarray analysis was performed to assess gene expression profiles.
- Cells were treated with 12-O-tetradecanoylphorbol-13-acetate (TPA) to observe gene expression changes.
Main Results:
- Distinct gene expression patterns were observed in Jnk1(-/-) and Jnk2(-/-) cells compared to wild-type.
- TPA treatment led to differential changes in gene expression profiles across the three cell types.
- These gene expression changes correlated with the observed differences in tumor susceptibility in the respective animal models.
Conclusions:
- JNK1 and JNK2 proteins possess non-redundant functions in modulating cellular processes.
- The distinct roles of JNK1 and JNK2 are reflected in their differential impact on gene expression and tumorigenesis.
