Identification of candidate cancer-causing genes in mouse brain tumors by retroviral tagging
| Autor: | Fredrik Johansson, Josefin Brodd, Bengt Westermark, Charlotta Eklöf, Maria Ferletta, Lene Uhrbom, Göran Hesselager, Carl-Fredrik Tiger |
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| Rok vydání: | 2004 |
| Předmět: |
Candidate gene
Mutagenesis (molecular biology technique) medicine.disease_cause Genome Insertional mutagenesis Mice Murine leukemia virus medicine Animals Gene Genetics Multidisciplinary biology Brain Neoplasms Cancer Glioma Proto-Oncogene Proteins c-sis Biological Sciences biology.organism_classification medicine.disease Mice Mutant Strains Gene Expression Regulation Neoplastic Mice Inbred C57BL Mutagenesis Insertional Cell Transformation Neoplastic Animals Newborn Moloney murine leukemia virus Carcinogenesis Signal Transduction |
| Zdroj: | Proceedings of the National Academy of Sciences. 101:11334-11337 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0402716101 |
| Popis: | Murine retroviruses may cause malignant tumors in mice by insertional mutagenesis of host genes. The use of retroviral tagging as a means of identifying cancer-causing genes has, however, almost entirely been restricted to hematopoietic tumors. The aim of this study was to develop a system allowing for the retroviral tagging of candidate genes in malignant brain tumors. Mouse gliomas were induced by a recombinant Moloney murine leukemia virus encoding platelet-derived growth factor (PDGF) B-chain. The underlying idea was that tumors evolve through a combination of PDGF-mediated autocrine growth stimulation and insertional mutagenesis of genes that cooperate with PDGF in gliomagenesis. Common insertion sites (loci that were tagged in more than one tumor) were identified by cloning and sequencing retroviral flanking segments, followed by blast searches of mouse genome databases. A number of candidate brain tumor loci (Btls) were identified. Several of these Btls correspond to known tumor-causing genes; these findings strongly support the underlying idea of our experimental approach. Other Btls harbor genes with a hitherto unproven role in transformation or oncogenesis. Our findings indicate that retroviral tagging with a growth factor-encoding virus may be a powerful means of identifying candidate tumor-causing genes in nonhematopoietic tumors. |
| Databáze: | OpenAIRE |
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