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Creation of human tumour cells with defined genetic elements.

Publication ,  Journal Article
Hahn, WC; Counter, CM; Lundberg, AS; Beijersbergen, RL; Brooks, MW; Weinberg, RA
Published in: Nature
July 29, 1999

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.

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Published In

Nature

DOI

ISSN

0028-0836

Publication Date

July 29, 1999

Volume

400

Issue

6743

Start / End Page

464 / 468

Location

England

Related Subject Headings

  • Telomere
  • Telomerase
  • RNA
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Humans
  • Genes, ras
  • General Science & Technology
 

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Hahn, W. C., Counter, C. M., Lundberg, A. S., Beijersbergen, R. L., Brooks, M. W., & Weinberg, R. A. (1999). Creation of human tumour cells with defined genetic elements. Nature, 400(6743), 464–468. https://doi.org/10.1038/22780
Hahn, W. C., C. M. Counter, A. S. Lundberg, R. L. Beijersbergen, M. W. Brooks, and R. A. Weinberg. “Creation of human tumour cells with defined genetic elements.Nature 400, no. 6743 (July 29, 1999): 464–68. https://doi.org/10.1038/22780.
Hahn WC, Counter CM, Lundberg AS, Beijersbergen RL, Brooks MW, Weinberg RA. Creation of human tumour cells with defined genetic elements. Nature. 1999 Jul 29;400(6743):464–8.
Hahn, W. C., et al. “Creation of human tumour cells with defined genetic elements.Nature, vol. 400, no. 6743, July 1999, pp. 464–68. Pubmed, doi:10.1038/22780.
Hahn WC, Counter CM, Lundberg AS, Beijersbergen RL, Brooks MW, Weinberg RA. Creation of human tumour cells with defined genetic elements. Nature. 1999 Jul 29;400(6743):464–468.
Journal cover image

Published In

Nature

DOI

ISSN

0028-0836

Publication Date

July 29, 1999

Volume

400

Issue

6743

Start / End Page

464 / 468

Location

England

Related Subject Headings

  • Telomere
  • Telomerase
  • RNA
  • Neoplasm Transplantation
  • Mice, Nude
  • Mice, Inbred BALB C
  • Mice
  • Humans
  • Genes, ras
  • General Science & Technology