Creation of human tumour cells with defined genetic elements.

Journal Article

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 oncogenes. However, similar experiments with human cells have consistently failed to yield tumorigenic transformants, 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 immortalization, the selection of rare, spontaneously arising immortalized cells, or the use of an entire viral genome. We show here that the ectopic expression of the telomerase catalytic subunit (hTERT) 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.

Full Text

Duke Authors

Cited Authors

  • Hahn, WC; Counter, CM; Lundberg, AS; Beijersbergen, RL; Brooks, MW; Weinberg, RA

Published Date

  • July 29, 1999

Published In

Volume / Issue

  • 400 / 6743

Start / End Page

  • 464 - 468

PubMed ID

  • 10440377

International Standard Serial Number (ISSN)

  • 0028-0836

Digital Object Identifier (DOI)

  • 10.1038/22780

Language

  • eng

Conference Location

  • England