Tumor induction by an endogenous K-ras oncogene is highly dependent on cellular context.
We have targeted a K-ras allele in mouse embryonic stem (ES) cells to express a K-Ras(V12) oncoprotein along with a marker protein (beta-geo) from a single bicistronic transcript. Expression of this oncogenic allele requires removal of a knocked in STOP transcriptional cassette by Cre recombinase. P...
| Autores: | , , , , , , , |
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| Formato: | artículo |
| Fecha de publicación: | 2003 |
| País: | España |
| Recursos: | Instituto de Salud Carlos III (ISCIII) |
| Repositorio: | Repisalud |
| Idioma: | inglés |
| OAI Identifier: | oai:repisalud.isciii.es:20.500.12105/23091 |
| Acesso em linha: | https://hdl.handle.net/20.500.12105/23091 |
| Access Level: | acceso abierto |
| Palavra-chave: | Cell Transformation, Neoplastic Protein Serine-Threonine Kinases Animals Cell Division Cell Line, Transformed Cellular Senescence Chromosome Aberrations Cyclin-Dependent Kinase Inhibitor p16 Fibroblasts Gene Targeting Genes, ras Genetic Vectors MAP Kinase Signaling System Mice Mice, Transgenic Neoplasms Oncogene Protein p21(ras) Proto-Oncogene Proteins Proto-Oncogene Proteins c-akt Reverse Transcriptase Polymerase Chain Reaction Stem Cells Survival Rate Tumor Suppressor Protein p14ARF Tumor Suppressor Protein p53 |
| Resumo: | We have targeted a K-ras allele in mouse embryonic stem (ES) cells to express a K-Ras(V12) oncoprotein along with a marker protein (beta-geo) from a single bicistronic transcript. Expression of this oncogenic allele requires removal of a knocked in STOP transcriptional cassette by Cre recombinase. Primary mouse embryonic fibroblasts expressing this K-ras(V12) allele do not undergo proliferative senescence and proliferate as immortal cells. In mice, expression of K-ras(V12) throughout the body fails to induce unscheduled proliferation or other growth abnormalities for up to eight months. Only a percentage of K-ras(V12)-expressing lung bronchiolo-alveolar cells undergo malignant transformation leading to the formation of multiple adenomas and adenocarcinomas. These results indicate that neoplastic growth induced by an endogenous K-ras oncogene depends upon cellular context. |
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