| First Author | Yoshizuka N | Year | 2012 |
| Journal | Mol Cancer Res | Volume | 10 |
| Issue | 6 | Pages | 810-20 |
| PubMed ID | 22665523 | Mgi Jnum | J:205386 |
| Mgi Id | MGI:5544705 | Doi | 10.1158/1541-7786.MCR-11-0576 |
| Citation | Yoshizuka N, et al. (2012) PRAK suppresses oncogenic ras-induced hematopoietic cancer development by antagonizing the JNK pathway. Mol Cancer Res 10(6):810-20 |
| abstractText | 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, Emu-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-NH(2)-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. |
