1. Cooperation between STAT3 and c-Jun Suppresses Fas Transcription
- Author
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Laurie B. Owen-Schaub, Vladimir N. Ivanov, Regina Raz, David E. Levy, Ze'ev Ronai, Mikhail Krasilnikov, Curt M. Horvath, and Anindita Bhoumik
- Subjects
STAT3 Transcription Factor ,Transcriptional Activation ,Fas Ligand Protein ,Transcription, Genetic ,Proto-Oncogene Proteins c-jun ,Ultraviolet Rays ,Cell ,Apoptosis ,Response Elements ,Radiation Tolerance ,Fas ligand ,Mice ,Downregulation and upregulation ,Tumor Cells, Cultured ,medicine ,Animals ,Humans ,RNA, Messenger ,fas Receptor ,Promoter Regions, Genetic ,STAT3 ,Molecular Biology ,Melanoma ,Sequence Deletion ,Regulation of gene expression ,Membrane Glycoproteins ,biology ,c-jun ,Cancer cells--Growth ,DNA ,Cell Biology ,Fibroblasts ,Up-Regulation ,Cell biology ,DNA-Binding Proteins ,Transcription Factor AP-1 ,medicine.anatomical_structure ,Gene Expression Regulation ,Oncology ,Tumor progression ,Trans-Activators ,biology.protein ,Cancer research ,Cytology ,Protein Binding - Abstract
Decreased Fas expression during tumor progression often results in a loss of Fas-ligand (FasL)-mediated apoptosis. Human and mouse melanoma exhibit an inverse correlation between the degree of Fas cell surface expression, tumorigenicity, and metastatic capacity. The expression of dominant negative Stat3 or c-Jun in melanoma cells efficiently increased Fas expression and sensitized cells to FasL-induced apoptosis. Stat3+/- as well as c-Jun-/- cells exhibited increased Fas cell surface expression and higher sensitivity to FasL-mediated apoptosis. Suppression of Fas expression by Stat3 and c-Jun is uncoupled from Stat3-mediated transcriptional activation. Our findings indicate that Stat3 oncogenic activities could also be mediated through its cooperation with c-Jun, resulting in downregulation of Fas surface expression, which is implicated in the tumor's ability to resist therapy and metastasize.
- Published
- 2001
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