Journal
MOLECULAR CANCER RESEARCH
Volume 10, Issue 6, Pages 810-820Publisher
AMER ASSOC CANCER RESEARCH
DOI: 10.1158/1541-7786.MCR-11-0576
Keywords
-
Categories
Funding
- NIH [CA106768, CA131231, RR025744]
- NSF China [30828019]
Ask authors/readers for more resources
The p38 mitogen-activated protein kinase (MAPK) pathway regulates multiple physiologic and pathologic processes, including cancer development. PRAK, a p38 substrate protein kinase, has previously been implicated in the suppression of skin carcinogenesis. In the current study, we show that PRAK deletion accelerates hematopoietic cancer development in a mouse model harboring an oncogenic ras allele, E mu-N-Ras(G12D), specifically expressed in hematopoietic cells. Further investigation reveals that enhanced hematopoietic tumorigenesis by PRAK deficiency is associated with hyperactivation of the c-jun-NH2-kinase (JNK) pathway both in vivo and in primary hematopoietic cells isolated from spleens. In primary splenocytes, PRAK deficiency further enhanced oncogenic ras-induced cell proliferation and promoted ras-mediated colony formation on semisolid medium in a JNK-dependent manner. In addition, deletion of PRAK leads to abrogation of ras-induced accumulation of senescence markers. These findings indicate that PRAK suppresses hematopoietic cancer formation in this mouse model by antagonizing oncogenic ras-induced activation of the JNK pathway. Our results suggest that PRAK may function as a tumor suppressor in multiple types of cancers. Mol Cancer Res; 10(6); 810-20. (C) 2012 AACR.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available