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JNK Regulates HIPK3 Expression and Promotes Resistance to Fas-mediated Apoptosis in DU 145 Prostate Carcinoma Cells

Overview of attention for article published in Journal of Biological Chemistry, April 2004
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Title
JNK Regulates HIPK3 Expression and Promotes Resistance to Fas-mediated Apoptosis in DU 145 Prostate Carcinoma Cells
Published in
Journal of Biological Chemistry, April 2004
DOI 10.1074/jbc.m307629200
Pubmed ID
Authors

James F. Curtin, Thomas G. Cotter

Abstract

Elevated endogenous JNK activity and resistance to Fas receptor-mediated apoptosis have recently been implicated in progression of prostate cancer and can promote resistance to apoptosis in response to chemotherapeutic drugs. In addition, JNK has been demonstrated to promote transformation of epithelial cells by increasing both proliferation and survival. Although numerous studies have reported a role for JNK in promoting Fas receptor-mediated apoptosis, there is a paucity in the literature studying the antiapoptotic function of JNK during Fas receptor-mediated apoptosis. Consequently, we have used the recently described specific JNK inhibitor SP600125 and RNA interference to inhibit endogenous JNK activity in the prostate carcinoma cell line DU 145. We demonstrated that endogenous JNK activity increased the expression of a kinase, HIPK3, that has previously been implicated in multidrug resistance in a number of tumors. HIPK3 has also been reported to phosphorylate FADD. The interaction between FADD and caspase-8 was inhibited, but abrogation of JNK activity or HIPK3 expression was found to restore this interaction and increased the sensitivity of DU 145 cells to Fas receptor-mediated apoptosis. In conclusion, we present novel evidence that JNK regulates the expression of HIPK3 in prostate cancer cells, and this contributes to increased resistance to Fas receptor-mediated apoptosis by reducing the interaction between FADD and caspase-8.

Mendeley readers

The data shown below were compiled from readership statistics for 37 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United Kingdom 1 3%
United States 1 3%
Unknown 35 95%

Demographic breakdown

Readers by professional status Count As %
Researcher 9 24%
Student > Ph. D. Student 9 24%
Professor 4 11%
Student > Master 4 11%
Professor > Associate Professor 3 8%
Other 5 14%
Unknown 3 8%
Readers by discipline Count As %
Agricultural and Biological Sciences 16 43%
Biochemistry, Genetics and Molecular Biology 13 35%
Medicine and Dentistry 3 8%
Computer Science 1 3%
Unknown 4 11%