title: c-Jun promotes whereas JunB inhibits epidermal neoplasia.
abstract: 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.affiliation: Department of Dermatology, Duke University, Durham, North Carolina 27710-0001, USA.
authors.forename: Jane Y
authors.initials: JY
authors.lastname: Jin
authors.forename: Hengning
authors.initials: H
authors.lastname: Ke
authors.forename: Russell P
authors.initials: RP
authors.lastname: Hall
authors.forename: Jennifer Y
authors.initials: JY
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D018929:Cell Culture Techniques; D002454:Cell Differentiation; D016922:Cellular Senescence; D051358:Cyclin-Dependent Kinase 4 / Q000378:metabolism; D019941:Cyclin-Dependent Kinase Inhibitor p16; D015536:Down-Regulation; D000091344:Filaggrin Proteins; D006801:Humans; D007381:Intermediate Filament Proteins / Q000378:metabolism; D008297:Male; D051379:Mice; D009363:Neoplasm Proteins / Q000378:metabolism; D015689:Oncogene Protein p21(ras) / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism*; D012867:Skin / Q000378:metabolism; D012878:Skin Neoplasms / Q000378:metabolism* / Q000473:pathology; D016038:Skin Transplantation / Q000473:pathology; D018808:Transcription Factor AP-1 / Q000378:metabolism; D015854:Up-Regulation
chemical_list: C000614131:CDKN2A protein, human; D019941:Cyclin-Dependent Kinase Inhibitor p16; C000717249:FLG protein, human; D000091344:Filaggrin Proteins; D007381:Intermediate Filament Proteins; D009363:Neoplasm Proteins; D016755:Proto-Oncogene Proteins c-jun; D018808:Transcription Factor AP-1; C495900:CDK4 protein, human; D051358:Cyclin-Dependent Kinase 4; D015689:Oncogene Protein p21(ras)