BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
BACKGROUND & AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.
Authors: Jen Jen Yeh; Elizabeth D Routh; Tara Rubinas; Janie Peacock; Timothy D Martin; Xiang Jun Shen; Robert S Sandler; Hong Jin Kim; Temitope O Keku; Channing J Der Journal: Mol Cancer Ther Date: 2009-04 Impact factor: 6.261
Authors: Shelly R Calcagno; Shuhua Li; Migdalisel Colon; Pamela A Kreinest; E Aubrey Thompson; Alan P Fields; Nicole R Murray Journal: Int J Cancer Date: 2008-06-01 Impact factor: 7.396
Authors: Liu Yang; Ying Wang; Hua Mao; Susanne Fleig; Alessia Omenetti; Kevin D Brown; Jason K Sicklick; Yin-Xiong Li; Anna Mae Diehl Journal: J Hepatol Date: 2007-10-18 Impact factor: 25.083
Authors: Géraldine Ibarz; Catherine Oiry; Eric Carnazzi; Philippe Crespy; Chantal Escrieut; Daniel Fourmy; Jean Claude Galleyrand; Didier Gagne; Jean Martinez Journal: Br J Pharmacol Date: 2006-04 Impact factor: 8.739