Creation of human tumour cells with defined genetic elements
| Autor: | Christopher M. Counter, Ante S. Lundberg, Roderick L. Beijersbergen, Robert A. Weinberg, Mary W. Brooks, William C. Hahn |
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| Rok vydání: | 1999 |
| Předmět: |
Telomerase
Cell division Antigens Polyomavirus Transforming Mice Nude Biology Cell Line Malignant transformation Mice Cell Adhesion Animals Humans Telomerase reverse transcriptase PINX1 Cells Cultured Genetics Mice Inbred BALB C Multidisciplinary Epithelial Cells Fibroblasts Telomere Cell biology DNA-Binding Proteins Cell Transformation Neoplastic Genes ras Cell culture Cancer cell RNA Cell Division Neoplasm Transplantation |
| Zdroj: | Nature. 400:464-468 |
| ISSN: | 1476-4687 0028-0836 |
| DOI: | 10.1038/22780 |
| Popis: | During malignant transformation, cancer cells acquire genetic mutations that override the normal mechanisms controlling cellular proliferation. Primary rodent cells are efficiently converted into tumorigenic cells by the coexpression of cooperating oncogenes1,2. However, similar experiments with human cells have consistently failed to yield tumorigenic transformants3,4,5, indicating a fundamental difference in the biology of human and rodent cells. The few reported successes in the creation of human tumour cells have depended on the use of chemical or physical agents to achieve immortalization6, the selection of rare, spontaneously arising immortalized cells7,8,9,10, or the use of an entire viral genome11. We show here that the ectopic expression of the telomerase catalytic subunit (hTERT)12 in combination with two oncogenes (the simian virus 40 large-T oncoprotein and an oncogenic allele of H-ras) results in direct tumorigenic conversion of normal human epithelial and fibroblast cells. These results demonstrate that disruption of the intracellular pathways regulated by large-T, oncogenic ras and telomerase suffices to create a human tumor cell. |
| Databáze: | OpenAIRE |
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