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Suppression of skin tumorigenesis in c-Jun NH(2)-terminal kinase-2-deficient mice
1The Hormel Institute, University of Minnesota, 801 16th Avenue NE, Austin, MN 55912, USA.
Abstract:
Previous studies have shown that c-Jun NH(2)-terminal kinase (JNK) belongs to the mitogen-activated protein kinase (MAPK) family of signal transduction components that are rapidly initiated and activated by many extracellular stimuli. However, the potential role of JNK in mediating tumor promotion and carcinogenesis is unclear. We show here that in JNK2-deficient (Jnk2(-/-)) mice, the multiplicity of papillomas induced by 12-O-tetradecanoylphorbol-13-acetate (TPA) was lower than that in wild-type mice. Papillomas on wild-type mice grew rapidly and were well vascularized compared with Jnk2(-/-) mice. After the 12th week of TPA treatment, the mean number of tumors per mouse was 4.13-4.86 in wild-type mice but only 1.13-2.5 in Jnk2(-/-) mice. TPA induced phosphorylation of extracellular signal-regulated kinases and activator protein-1 DNA binding activity in wild-type mice, but the phosphorylation of extracellular signal-regulated kinases and activator protein-1 DNA binding were inhibited in Jnk2(-/-) mice. These data suggest that JNK2 is critical in the tumor promotion process.
Insights
The study reveals that JNK2 deficiency in mice significantly reduces tumor promotion caused by 12-O-tetradecanoylphorbol-13-acetate (TPA). This highlights JNK2
Area of Science:
- Molecular Biology
- Oncology
- Signal Transduction
Background:
- c-Jun NH(2)-terminal kinase (JNK) is a mitogen-activated protein kinase (MAPK) involved in cellular responses to stimuli.
- The specific role of JNK in tumor promotion and carcinogenesis remains incompletely understood.
Purpose of the Study:
- To investigate the role of JNK2 in mediating tumor promotion and carcinogenesis.
- To determine the impact of JNK2 deficiency on chemically induced skin tumors.
Main Methods:
- Comparison of tumor development in JNK2-deficient (Jnk2(-/-)) mice and wild-type mice following 12-O-tetradecanoylphorbol-13-acetate (TPA) treatment.
- Assessment of papilloma multiplicity, growth, and vascularization.
- Analysis of TPA-induced phosphorylation of extracellular signal-regulated kinases and activator protein-1 DNA binding activity.
Main Results:
- JNK2-deficient mice exhibited significantly lower papilloma multiplicity compared to wild-type mice after TPA treatment.
- Papillomas in wild-type mice showed more rapid growth and better vascularization than those in JNK2-deficient mice.
- TPA-induced phosphorylation of extracellular signal-regulated kinases and activator protein-1 DNA binding activity were suppressed in JNK2-deficient mice.
Conclusions:
- JNK2 plays a critical role in the tumor promotion process.
- JNK2 signaling is essential for mediating the effects of TPA in skin carcinogenesis.