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Gastroenterology. 1997 Nov;113(5):1589-98.

In vivo activation of mitogen-activated protein kinases in rat intestinal neoplasia.

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Department of Microbiology and Immunology, University of North Carolina at Chapel Hill 27599, USA.



To investigate whether mitogen-activated protein kinase (MAPK) cascades might play a role in the progression of colon cancer, c-Jun N-terminal kinase (JNK) and extracellular signal regulating kinase (ERK) activity during colonic tumorigenesis were examined.


The 1,2-dimethylhydrazine (DMH)-induced colon carcinoma model was used to study the activation of these kinases during intestinal carcinogenesis. Male Sprague-Dawley rats were injected with DMH for 24 weeks. Normal-appearing intestinal mucosa from control and treated animals and DMH-induced intestinal tumors were assayed for JNK and ERK activity using solid phase in vitro kinase assays. Tumors were typed for mutations in the K-ras gene.


There was little or no difference in JNK and ERK activity in hyperproliferative mucosa from DMH-treated animals compared with normal mucosa from control animals. However, in 16 colonic neoplasms, an average of 23-fold and 29-fold increases in JNK and ERK activities were observed, respectively, over control levels. In addition, activating protein-1 binding was strongly induced in the colonic tumors. Activation did not correlate with the presence of mutations in K-ras.


Both the JNK and ERK MAPKs are highly activated during late progression of colorectal carcinoma. This change is dependent on the tumorigenic state rather than changes in proliferation.

[Indexed for MEDLINE]

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