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Journal article
Mammary Gland Selective Excision of c-Jun Identifies Its Role in mRNA Splicing
Cancer research (Chicago, Ill.), v 72(4), pp 1023-1034
15 Feb 2012
PMID: 22174367
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
The c-jun gene regulates cellular proliferation and apoptosis via direct regulation of cellular gene expression. Alternative splicing of pre-mRNA increases the diversity of protein functions, and alternate splicing events occur in tumors. Here, by targeting the excision of the endogenous c-jun gene within the mouse mammary epithelium, we have identified its selective role as an inhibitor of RNA splicing. Microarray-based assessment of gene expression, on laser capture microdissected c-jun(-/-) mammary epithelium, showed that endogenous c-jun regulates the expression of approximately 50 genes governing RNA splicing. In addition, genome-wide splicing arrays showed that endogenous c-jun regulated the alternate exon of approximately 147 genes, and 18% of these were either alternatively spliced in human tumors or involved in apoptosis. Endogenous c-jun also was shown to reduce splicing activity, which required the c-jun dimerization domain. Together, our findings suggest that c-jun directly attenuates RNA splicing efficiency, which may be of broad biologic importance as alternative splicing plays an important role in both cancer development and therapy resistance. Cancer Res; 72(4); 1023-34. (C) 2011 AACR.
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Details
- Title
- Mammary Gland Selective Excision of c-Jun Identifies Its Role in mRNA Splicing
- Creators
- Sanjay Katiyar - Thomas Jefferson UniversityXuanmao Jiao - Thomas Jefferson UniversitySankar Addya - Thomas Jefferson UniversityAdam Ertel - Thomas Jefferson UniversityYolanda Covarrubias - Thomas Jefferson UniversityVanessa Rose - Thomas Jefferson UniversityMathew C. Casimiro - Thomas Jefferson UniversityJie Zhou - Thomas Jefferson UniversityMichael P. Lisanti - Thomas Jefferson UniversityTalat Nasim - Kings Coll London, Guys & St Thomas NHS Fdn Trust, Dept Med & Mol Genet, London WC2R 2LS, EnglandPaolo Fortina - Thomas Jefferson UniversityRichard G. Pestell - Thomas Jefferson University
- Publication Details
- Cancer research (Chicago, Ill.), v 72(4), pp 1023-1034
- Publisher
- Amer Assoc Cancer Research
- Number of pages
- 12
- Grant note
- Marian C. Falk Medical Research Trust Pennsylvania Department of Health R01CA070896; R01CA075503; R01CA107382; R01CA132115; R01CA086072; R01CA120876 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01CA132115 / NATIONAL CANCER INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P30CA056036 / NIH Cancer Center; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- School of Biomedical Engineering, Science, and Health Systems
- Web of Science ID
- WOS:000300629100021
- Scopus ID
- 2-s2.0-84863152361
- Other Identifier
- 991019176802904721
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- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Oncology