Document Detail


c-Jun promotes whereas JunB inhibits epidermal neoplasia.
MedLine Citation:
PMID:  21289643     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Deregulation of the activator protein 1 (AP1) family gene regulators has been implicated in a wide range of diseases, including cancer. In this study we report that c-Jun was activated in human squamous cell carcinoma (SCC) and coexpression of c-Jun with oncogenic Ras was sufficient to transform primary human epidermal cells into malignancy in a regenerated human skin grafting model. In contrast, JunB was not induced in a majority of human SCC cells. Moreover, exogenous expression of JunB inhibited tumorigenesis driven by Ras or spontaneous human SCC cells. Conversely, the dominant-negative JunB mutant (DNJunB) promoted tumorigenesis, which is in contrast to the tumor-suppressor function of the corresponding c-Jun mutant. At the cellular level, JunB induced epidermal cell senescence and slowed cell growth in a cell-autonomous manner. Consistently, coexpression of JunB and Ras induced premature epidermal differentiation concomitant with upregulation of p16 and filaggrin and downregulation of cyclin D1 and cyclin-dependent kinase 4 (CDK4). These findings indicate that JunB and c-Jun differentially regulate cell growth and differentiation and induce opposite effects on epidermal neoplasia.JID JOURNAL CLUB ARTICLE: For questions, answers, and open discussion about this article, please go to http://www.nature.com/jid/journalclub.
Authors:
Jane Y Jin; Hengning Ke; Russell P Hall; Jennifer Y Zhang
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2011-02-03
Journal Detail:
Title:  The Journal of investigative dermatology     Volume:  131     ISSN:  1523-1747     ISO Abbreviation:  J. Invest. Dermatol.     Publication Date:  2011 May 
Date Detail:
Created Date:  2011-04-15     Completed Date:  2011-07-14     Revised Date:  2014-09-11    
Medline Journal Info:
Nlm Unique ID:  0426720     Medline TA:  J Invest Dermatol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1149-58     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Carcinoma, Squamous Cell / metabolism*,  pathology
Cell Aging
Cell Culture Techniques
Cell Differentiation
Cyclin-Dependent Kinase 4 / metabolism
Down-Regulation
Humans
Intermediate Filament Proteins / metabolism
Male
Mice
Neoplasm Proteins / metabolism
Oncogene Protein p21(ras) / metabolism*
Proto-Oncogene Proteins c-jun / metabolism*
Skin / metabolism
Skin Neoplasms / metabolism*,  pathology
Skin Transplantation / pathology
Transcription Factor AP-1 / metabolism
Up-Regulation
Grant Support
ID/Acronym/Agency:
K01 AR051470/AR/NIAMS NIH HHS; K01 AR051470-04/AR/NIAMS NIH HHS; K01 AR051470-05/AR/NIAMS NIH HHS; K01AR051470/AR/NIAMS NIH HHS; R01 AR057746/AR/NIAMS NIH HHS; R01 AR057746-01A1/AR/NIAMS NIH HHS; R01AR57746/AR/NIAMS NIH HHS
Chemical
Reg. No./Substance:
0/Intermediate Filament Proteins; 0/Neoplasm Proteins; 0/P16 protein, human; 0/Proto-Oncogene Proteins c-jun; 0/Transcription Factor AP-1; 0/filaggrin; EC 2.7.11.22/CDK4 protein, human; EC 2.7.11.22/Cyclin-Dependent Kinase 4; EC 3.6.5.2/Oncogene Protein p21(ras)
Comments/Corrections
Comment In:
J Invest Dermatol. 2011 May;131(5):1002   [PMID:  21494238 ]
Erratum In:
J Invest Dermatol. 2011 Jun;131(6):1388

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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