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Basic Sciences

Transformation of Normal Homologous Cells by a Spontaneously Activated Ha-ras Oncogene

Stephen A. Schwartz, Charles F. Shuler and Peter Freebeck
Stephen A. Schwartz
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Charles F. Shuler
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Peter Freebeck
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DOI:  Published June 1988
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Abstract

Several tumor-derived oncogenes have been shown to independently act as complete carcinogens following transfection into target cells from established tissue culture lines. However, the number and types of oncogenes required to transform primary cultures of normal mammalian cells is unclear. To clarify this issue in a simplified model system, we transfected genomic DNA from a naturally occurring rat tumor into NIH/3T3 cells as well as into early passage rat embryo fibroblasts. The 3T3 cells were transformed with high efficiency to malignant phenotypes; the rat embryo cells were transformed at lower frequencies following cotransfection with a selectable neomycin resistance marker and treatment with Geneticin (G418). The transformed rat cells had cancerous phenotypes as determined by in vitro, cytogenetic, and in vivo criteria. Moreover, the transformed mouse and rat cells contained new tumor DNA-derived nucleotide sequences homologous to the activated human Ha-ras oncogene. Elevated levels of Ha-ras-specific mRNA, as well as enhanced expression of the Mr 21,000 oncogene product, were detected in the transformed cells. Therefore, under well-defined experimental conditions, a spontaneously activated Ha-ras oncogene from a naturally occurring tumor was able to independently transform normal, homologous cells to a malignant phenotype.

Footnotes

  • ↵1 This work was supported by Research Grant 84-14 from the American Cancer Society, Illinois Division, Research Grant DE-04970 from the NIH, and BRSG S07 RR05366-24, Division of Research Resources, NIH.

  • Received March 10, 1986.
  • Revision received November 7, 1986.
  • Revision received December 17, 1987.
  • Accepted March 3, 1988.
  • ©1988 American Association for Cancer Research.
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June 1988
Volume 48, Issue 12
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Transformation of Normal Homologous Cells by a Spontaneously Activated Ha-ras Oncogene
Stephen A. Schwartz, Charles F. Shuler and Peter Freebeck
Cancer Res June 15 1988 (48) (12) 3470-3477;

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Transformation of Normal Homologous Cells by a Spontaneously Activated Ha-ras Oncogene
Stephen A. Schwartz, Charles F. Shuler and Peter Freebeck
Cancer Res June 15 1988 (48) (12) 3470-3477;
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