Skip Navigation



Carcinogenesis Advance Access published online on December 4, 2008
Carcinogenesis, doi:10.1093/carcin/bgn271
This Article
Right arrow Advance Access manuscript (PDF)
Right arrow All Versions of this Article:
30/2/222    most recent
bgn271v1
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Wang, J.
Right arrow Articles by Wong, B. C.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Wang, J.
Right arrow Articles by Wong, B. C.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

© The Author 2008. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oxfordjournals.org

c-jun NH2-terminal Kinase (JNK1) Upregulates XIAP-associated Factor 1 (XAF1) through Interferon Regulatory Factor 1 (IRF-1) in Gastrointestinal Cancer

Jide Wang1,2,*, Wenjing Zhang1,2, Yusheng Zhang1,2, Ye Chen1, Bing Zou2, Bo Jiang1, Roberta Pang2, Qing Gu2, Liang Qiao2, Huiyao Lan2, Hsiang-Fu Kung3 and Benjamin CY Wong2,*

1 Department of Digestive Medicine, Nanfang Hospital, the Southern Medical University, Guangzhou, China
2 Department of Medicine, University of Hong Kong, Hong Kong
3 The Center for Emerging Infectious Diseases, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong

* Corresponding Author: Dr. Benjamin CY Wong: Department of Medicine, University of Hong Kong, Queen Mary Hospital, Hong Kong. Tel: 852-28555995; Fax: 852-29049443; E-mail: bcywong{at}hku.hk, Dr. Jide Wang: Department of Digestive Medicine, Nanfang Hospital, the Southern Medical University, Guangzhou 510515, China. Tel: 86-20-61641538; Fax: 86-20-87280770; Email: jidewang{at}gmail.com

Background & Aims: XIAP associated factor 1 (XAF1) is a tumor suppressor that can sensitize cancer cell to apoptosis. Intrinsic expression of XAF1 in cancer cell is low. Our purpose is to determine the effect of c-jun NH2-terminal kinase 1 (JNK1) on XAF1 expression and the putative mechanism.

Methods: XAF1 expression in gastrointestinal (GI) cancer cell line AGS and SW1116 was detected by RT-PCR, real time PCR and immunoblotting. The role of JNK1 was assessed by ectopic over-expression with wildtype (JNK1-WT) and dominant negative (JNK1-DN) JNK1 constructs. The effects of JNK1 activator, IFN-{alpha}, TNF-{alpha} and PMA or JNK1 inhibitor, SP600125 were evaluated. An XAF1 promoter reporter pLUC107 with wildtype or mutated interferon regulatory factor 1 (IRF-1) binding element (IRF-E) was used to assess JNK1-induced transcription by dual-luciferase assay.

Result: Ectopic over-expression of JNK1-WT or treatment with IFN-{alpha}, TNF-{alpha} and PMA induced while SP600125 suppressed intrinsic and induced XAF1 expression. Induction of XAF1 required de novo protein synthesis. Moreover, JNK1 stimulated while SP600125 suppressed XAF1 promoter activity. JNK1 stimulated IRF-1 expression, while both IRF-1 siRNA and site mutation of IRF-E within XAF1 promoter abrogated the effect of JNK1.

Conclusion: JNK1 stimulated and mediated the effects of IFN and TNF-{alpha} on XAF1 expression through transcriptional regulation by induction of IRF-1. The linkage of JNK1, IRF-1 and XAF1 in the same signal pathway may unravel a novel mechanism in regulation of apoptosis and differentiation of GI cancers.

Key Words: c-jun NH2-terminal Kinase (JNK1) • Upregulates XIAP-associated Factor 1 (XAF1) • Interferon Regulatory Factor 1 (IRF-1) • Gastrointestinal Cancer

Received July 1, 2008; revised November 14, 2008; accepted November 29, 2008.


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?




Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.