title: MiniSOX9, a dominant-negative variant in colon cancer cells.
abstract: Inherited and acquired changes in pre-mRNA processing have significant roles in human diseases, especially cancer. Characterization of aberrantly spliced mRNAs may thus contribute to understand malignant transformation. We recently reported an anti-oncogenic potential for the SOX9 transcription factor in the colon. For instance, the Sox9 gene knock out in the mouse intestine results in an excess of proliferation with appearance of hyperplasia. SOX9 is expressed in colon cancer cells but its endogenous activity is weak. We looked for SOX9 variants that may impair SOX9 activity in colon cancer cells and we discovered MiniSOX9, a truncated version of SOX9 devoid of transactivation domain as a result of retention of the second intron. A significant overexpression of MiniSOX9 mRNA in human tumor samples compared with their matched normal tissues was observed by real-time reverse transcriptase-PCR. Immunohistochemistry revealed that MiniSOX9 is expressed at high levels in human colon cancer samples whereas it is undetectable in the surrounding healthy tissues. Finally, we discovered that MiniSOX9 behaves as a SOX9 inhibitor, inhibits protein kinase Cα promoter activity and stimulates the canonical Wnt pathway. This potential oncogenic activity of the SOX9 locus gives new insights on its role in colon cancer.
authors.affiliation: Institut de Génomique Fonctionnelle, Montpellier, France.
authors.forename: R
authors.initials: R
authors.lastname: Abdel-Samad
authors.forename: H
authors.initials: H
authors.lastname: Zalzali
authors.forename: C
authors.initials: C
authors.lastname: Rammah
authors.forename: J
authors.initials: J
authors.lastname: Giraud
authors.forename: C
authors.initials: C
authors.lastname: Naudin
authors.forename: S
authors.initials: S
authors.lastname: Dupasquier
authors.forename: F
authors.initials: F
authors.lastname: Poulat
authors.forename: B
authors.initials: B
authors.lastname: Boizet-Bonhoure
authors.forename: S
authors.initials: S
authors.lastname: Lumbroso
authors.forename: K
authors.initials: K
authors.lastname: Mouzat
authors.forename: C
authors.initials: C
authors.lastname: Bonnans
authors.forename: C
authors.initials: C
authors.lastname: Pignodel
authors.forename: P
authors.initials: P
authors.lastname: Raynaud
authors.forename: P
authors.initials: P
authors.lastname: Fort
authors.forename: C
authors.initials: C
authors.lastname: Quittau-Prévostel
authors.forename: P
authors.initials: P
authors.lastname: Blache
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D005799:Genes, Dominant; D006801:Humans; D007438:Introns; D051379:Mice; D008817:Mice, Mutant Strains; D008969:Molecular Sequence Data; D009154:Mutation; D011401:Promoter Regions, Genetic; D051571:Protein Kinase C-alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D055758:SOX9 Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D051153:Wnt Proteins / Q000378:metabolism
chemical_list: D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C527933:Sox9 protein, mouse; D051153:Wnt Proteins; D051571:Protein Kinase C-alpha