Creation of human tumour cells with defined genetic elements View Full Text


Ontology type: schema:ScholarlyArticle     


Article Info

DATE

1999-07

AUTHORS

William C. Hahn, Christopher M. Counter, Ante S. Lundberg, Roderick L. Beijersbergen, Mary W. Brooks, Robert A. Weinberg

ABSTRACT

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. More... »

PAGES

464-468

Journal

TITLE

Nature

ISSUE

6743

VOLUME

400

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/22780

    DOI

    http://dx.doi.org/10.1038/22780

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1021312708

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/10440377


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