1. A new mechanism of SOX9 action to regulate PKCα expression in the intestine epithelium
- Author
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Corinne Quittau-Prévostel, Vincent Cavaillès, Robert I. Glazer, Philippe Jay, Rana Abdel-Samad, Dominique Joubert, Sébastien Dupasquier, Pauline Bastide, Philippe Blache, Institut National de la Santé et de la Recherche Médicale (INSERM), Centre National de la Recherche Scientifique (CNRS), and Université de Montpellier (UM)
- Subjects
MESH: Signal Transduction ,MESH: Adenomatous Polyposis Coli Protein ,endocrine system ,Protein Kinase C-alpha ,Transcription, Genetic ,Sp1 Transcription Factor ,Adenomatous Polyposis Coli Protein ,[SDV.CAN]Life Sciences [q-bio]/Cancer ,SOX9 ,Biology ,Gene Expression Regulation, Enzymologic ,Cell Line ,MESH: SOX9 Transcription Factor ,03 medical and health sciences ,0302 clinical medicine ,Downregulation and upregulation ,MESH: RNA, Small Interfering ,medicine ,Animals ,Humans ,MESH: Animals ,SOX9 Transcription Factor ,Intestinal Mucosa ,RNA, Small Interfering ,Transcription factor ,Psychological repression ,Protein kinase C ,030304 developmental biology ,MESH: Sp1 Transcription Factor ,0303 health sciences ,MESH: Humans ,MESH: Gene Expression Regulation, Enzymologic ,MESH: Transcription, Genetic ,Epithelial Cells ,Cell Biology ,In vitro ,Epithelium ,MESH: Cell Line ,Cell biology ,MESH: Wnt Proteins ,Wnt Proteins ,medicine.anatomical_structure ,MESH: Epithelial Cells ,030220 oncology & carcinogenesis ,Immunology ,MESH: Intestinal Mucosa ,MESH: Protein Kinase C-alpha ,Signal Transduction - Abstract
International audience; Variations of protein kinase C (PKC) expression greatly influence the proliferation-to-differentiation transition (PDT) of intestinal epithelial cells and might have an important impact on intestinal tumorigenesis. We demonstrate here that the expression of PKCalpha in proliferating intestinal epithelial cells is repressed both in vitro and in vivo by the SOX9 transcription factor. This repression does not require DNA binding of the SOX9 high-mobility group (HMG) domain but is mediated through a new mechanism of SOX9 action requiring the central and highly conserved region of SOXE members. Because SOX9 expression is itself upregulated by Wnt-APC signaling in intestinal epithelial cells, the present study points out this transcription factor as a molecular link between the Wnt-APC pathway and PKCalpha. These results provide a potential explanation for the decrease of PKCalpha expression in colorectal cancers with constitutive activation of the Wnt-APC pathway.
- Published
- 2009
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