Open Access. Powered by Scholars. Published by Universities.®

Biochemistry, Biophysics, and Structural Biology Commons

Open Access. Powered by Scholars. Published by Universities.®

Articles 1 - 4 of 4

Full-Text Articles in Biochemistry, Biophysics, and Structural Biology

Inflammation Mediated By Jnk In Myeloid Cells Promotes The Development Of Hepatitis And Hepatocellular Carcinoma, Myoung Souk Han, Tamera Barrett, Michael A. Brehm, Roger J. Davis Apr 2016

Inflammation Mediated By Jnk In Myeloid Cells Promotes The Development Of Hepatitis And Hepatocellular Carcinoma, Myoung Souk Han, Tamera Barrett, Michael A. Brehm, Roger J. Davis

Davis Lab Publications

The cJun NH2-terminal kinase (JNK) signaling pathway is required for the development of hepatitis and hepatocellular carcinoma. A role for JNK in liver parenchymal cells has been proposed, but more recent studies have implicated non-parenchymal liver cells as the relevant site of JNK signaling. Here, we tested the hypothesis that myeloid cells mediate this function of JNK. We show that mice with myeloid cell-specific JNK deficiency exhibit reduced hepatic inflammation and suppression of both hepatitis and hepatocellular carcinoma. These data identify myeloid cells as a site of pro-inflammatory signaling by JNK that can promote liver pathology. Targeting myeloid cells with ...


Jnk And Pten Cooperatively Control The Development Of Invasive Adenocarcinoma Of The Prostate, Anette Hubner, David J. Mulholland, Claire L. Standen, Maria Karasarides, Julie Cavanagh-Kyros, Tamera Barrett, Hongbo Chi, Dale Greiner, Cathy Tournier, Charles L. Sawyers, Richard A. Flavell, Hong Wu, Roger J. Davis Jul 2012

Jnk And Pten Cooperatively Control The Development Of Invasive Adenocarcinoma Of The Prostate, Anette Hubner, David J. Mulholland, Claire L. Standen, Maria Karasarides, Julie Cavanagh-Kyros, Tamera Barrett, Hongbo Chi, Dale Greiner, Cathy Tournier, Charles L. Sawyers, Richard A. Flavell, Hong Wu, Roger J. Davis

Davis Lab Publications

The c-Jun NH(2)-terminal kinase (JNK) signal transduction pathway is implicated in cancer, but the role of JNK in tumorigenesis is poorly understood. Here, we demonstrate that the JNK signaling pathway reduces the development of invasive adenocarcinoma in the phosphatase and tensin homolog (Pten) conditional deletion model of prostate cancer. Mice with JNK deficiency in the prostate epithelium (DeltaJnk DeltaPten mice) develop androgen-independent metastatic prostate cancer more rapidly than control (DeltaPten) mice. Similarly, prevention of JNK activation in the prostate epithelium (DeltaMkk4 DeltaMkk7 DeltaPten mice) causes rapid development of invasive adenocarcinoma. We found that JNK signaling defects cause an ...


Requirement Of C-Jun Nh(2)-Terminal Kinase For Ras-Initiated Tumor Formation, Cristina Arrigo Cellurale, Guadalupe Sabio, Norman J. Kennedy, Madhumita Das, Marissa Bylsma, Peter Sandy, Tyler Jacks, Roger J. Davis Apr 2011

Requirement Of C-Jun Nh(2)-Terminal Kinase For Ras-Initiated Tumor Formation, Cristina Arrigo Cellurale, Guadalupe Sabio, Norman J. Kennedy, Madhumita Das, Marissa Bylsma, Peter Sandy, Tyler Jacks, Roger J. Davis

Davis Lab Publications

The c-Jun NH(2)-terminal kinase (JNK) signal transduction pathway causes increased gene expression mediated, in part, by members of the activating transcription factor protein (AP1) group. JNK is therefore implicated in the regulation of cell growth and cancer. To test the role of JNK in Ras-induced tumor formation, we examined the effect of compound ablation of the ubiquitously expressed genes Jnk1 plus Jnk2. We report that JNK is required for Ras-induced transformation of p53-deficient primary cells in vitro. Moreover, JNK is required for lung tumor development caused by mutational activation of the endogenous KRas gene in vivo. Together, these ...


The Role Of Jnk In The Development Of Hepatocellular Carcinoma, Madhumita Das, David S. Garlick, Dale Greiner, Roger J. Davis Mar 2011

The Role Of Jnk In The Development Of Hepatocellular Carcinoma, Madhumita Das, David S. Garlick, Dale Greiner, Roger J. Davis

Davis Lab Publications

The cJun NH(2)-terminal kinase (JNK) signal transduction pathway has been implicated in the growth of carcinogen-induced hepatocellular carcinoma. However, the mechanism that accounts for JNK-regulated tumor growth is unclear. Here we demonstrate that compound deficiency of the two ubiquitously expressed JNK isoforms (JNK1 and JNK2) in hepatocytes does not prevent hepatocellular carcinoma development. Indeed, JNK deficiency in hepatocytes increased the tumor burden. In contrast, compound JNK deficiency in hepatocytes and nonparenchymal cells reduced both hepatic inflammation and tumorigenesis. These data indicate that JNK plays a dual role in the development of hepatocellular carcinoma. JNK promotes an inflammatory hepatic ...