Runx1 is a tumor suppressor gene in the mouse gastrointestinal tract
| Autor: | A Rod, Michael G. O’Sullivan, Marianne Tijssen, Robert T. Cormier, Patricia M. Scott, Jieming Liu, Ethan Richards, Janae Anderson, Remond J.A. Fijneman, Gerrit A. Meijer, Rebecca Anderson |
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| Přispěvatelé: | Pathology, CCA - Oncogenesis |
| Rok vydání: | 2012 |
| Předmět: |
Male
Cancer Research Tumor suppressor gene Biology Real-Time Polymerase Chain Reaction medicine.disease_cause Mice Intestinal mucosa hemic and lymphatic diseases Conditional gene knockout medicine Animals Genes Tumor Suppressor Intestinal Mucosa Progenitor cell Tissue homeostasis Gastrointestinal Neoplasms Oligonucleotide Array Sequence Analysis Mice Knockout Gastrointestinal tract Reverse Transcriptase Polymerase Chain Reaction Gene Expression Profiling Stem Cells Original Articles General Medicine Gastrointestinal Tract Mice Inbred C57BL Oncology Core Binding Factor Alpha 2 Subunit embryonic structures Cancer research Female Stem cell Carcinogenesis |
| Zdroj: | Cancer Science, 103(3), 593-599. Wiley-Blackwell Fijneman, R J A, Anderson, R A, Richards, E, Liu, J, Tijssen, M, Meijer, G A, Anderson, J, Rod, A, O'Sullivan, MG, Scott, P M & Cormier, R T 2012, ' Runx1 is a tumor suppressor gene in the mouse gastrointestinal tract ', Cancer Science, vol. 103, no. 3, pp. 593-599 . https://doi.org/10.1111/j.1349-7006.2011.02189.x |
| ISSN: | 1347-9032 |
| DOI: | 10.1111/j.1349-7006.2011.02189.x |
| Popis: | The Runx1 transcription factor plays an important role in tissue homeostasis through its effects on stem/progenitor cell populations and differentiation. The effect of Runx1 on epithelial differentiation of the secretory cell lineage of the colon was recently demonstrated. This study aimed to examine the role of Runx1 in tumor development in epithelial cells of the gastrointestinal tract. Conditional knockout mice that lacked Runx1 expression in epithelial cells of the GI tract were generated. These mice were crossed onto the Apc Min background, killed and their intestinal tumor phenotypes were compared with Apc Min Runx1 wild‐type control mice. Apc‐wild‐type Runx1‐mutant mice were also examined for tumor development. Colons from Runx1 knockout and wild‐type mice were used for genome‐wide mRNA expression analyses followed by gene‐specific quantitative RT‐PCR of whole colon and colon epithelium to identify Runx1 target genes. Runx1 deficiency in intestinal epithelial cells significantly enhanced tumorigenesis in Apc Min mice. Notably, epithelial Runx1 deficiency in Apc‐wild‐type mice was sufficient to cause tumor development. Absence of Runx1 was associated with global changes in the expression of genes involved in inflammation and intestinal metabolism, and with gene sets indicative of a metastatic phenotype and poor prognosis. Gene‐specific analysis of Runx1‐deficient colon epithelium revealed increased expression of genes linked to an expansion of the stem/progenitor cell population. These results identify Runx1 as a novel tumor suppressor gene for gastrointestinal tumors and support a role for Runx1 in maintaining the balance between the intestinal stem/progenitor cell population and epithelial differentiation of the GI tract. (Cancer Sci 2012; 103: 593–599) |
| Databáze: | OpenAIRE |
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