MiniSOX9, a dominant-negative variant in colon cancer cells

被引：30

作者：

Abdel-Samad, R. ^{[1
,2
]}

Zalzali, H. ^{[1
,2
]}

Rammah, C. ^{[1
,2
]}

Giraud, J. ^{[1
,2
]}

Naudin, C. ^{[1
,2
]}

Dupasquier, S. ^{[1
,2
]}

Poulat, F. ^{[3
]}

Boizet-Bonhoure, B. ^{[3
]}

Lumbroso, S. ^{[4
]}

Mouzat, K. ^{[4
]}

Bonnans, C. ^{[1
,2
]}

Pignodel, C. ^{[5
]}

Raynaud, P. ^{[1
,2
]}

Fort, P. ^{[6
]}

Quittau-Prevostel, C. ^{[1
,2
]}

Blache, P. ^{[1
,2
]}

机构：

[1] Univ Montpellier 1, INSERM, CNRS, Inst Genom Fonct,UMR 5203,U661, F-34094 Montpellier 5, France

[2] Univ Montpellier 2, F-34094 Montpellier 5, France

[3] UPR, CNRS, Inst Genet Humaine, Montpellier, France

[4] CHU Nimes, Biochim Lab, Nimes, France

[5] CHU Nimes, Serv Anat & Cytol Pathol, Nimes, France

[6] CNRS, UMR 5237, Ctr Rech Biochim Macromol, Montpellier, France

来源：

ONCOGENE | 2011年 / 30卷 / 22期

关键词：

PKC alpha; SOX9; Wnt/beta-catenin signaling pathway; MESSENGER-RNA POLYADENYLATION; BETA-CATENIN; TRANSCRIPTION FACTOR; CAMPOMELIC DYSPLASIA; GENE-EXPRESSION; FACTOR SOX9; MOUSE; IDENTIFICATION; INHIBITION; EPITHELIUM;

D O I：

10.1038/onc.2010.621

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 C alpha 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. Oncogene (2011) 30, 2493-2503; doi:10.1038/onc.2010.621; published online 7 February 2011

引用

页码：2493 / 2503

页数：11

共 42 条

[1] RAR agonists stimulate SOX9 gene expression in breast cancer cell lines: evidence for a role in retinoid-mediated growth inhibition [J].