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Molecular and Cellular Biology, August 2005, p. 6464-6474, Vol. 25, No. 15
0270-7306/05/$08.00+0     doi:10.1128/MCB.25.15.6464-6474.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.

Transformation of Human and Murine Fibroblasts without Viral Oncoproteins

Jesse S. Boehm, Meghan T. Hession, Sara E. Bulmer, and William C. Hahn*

Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts 02115; Departments of Medicine and Pathology, Harvard Medical School, Boston, Massachusetts 02115; and Broad Institute of Harvard and MIT, Cambridge, Massachusetts 02139

Received 17 December 2004/ Returned for modification 25 February 2005/ Accepted 7 May 2005

Murine embryo fibroblasts are readily transformed by the introduction of specific combinations of oncogenes; however, the expression of those same oncogenes in human cells fails to convert such cells to tumorigenicity. Using normal human and murine embryonic fibroblasts, we show that the transformation of human cells requires several additional alterations beyond those required to transform comparable murine cells. The introduction of the c-Myc and H-RAS oncogenes in the setting of loss of p53 function efficiently transforms murine embryo fibroblasts but fails to transform human cells constitutively expressing hTERT, the catalytic subunit of telomerase. In contrast, transformation of multiple strains of human fibroblasts requires the constitutive expression of c-Myc, H-RAS, and hTERT, together with loss of function of the p53, RB, and PTEN tumor suppressor genes. These manipulations permit the development of transformed human fibroblasts with genetic alterations similar to those found associated with human cancers and define specific differences in the susceptibility of human and murine fibroblasts to experimental transformation.

* Corresponding author. Mailing address: Department of Medical Oncology, Dana-Farber Cancer Institute, 44 Binney St., Dana 710C, Boston, MA 02115-6013. Phone: (617) 632-2641. Fax: (617) 632-2375. E-mail: William_Hahn{at}dfci.harvard.edu.

Molecular and Cellular Biology, August 2005, p. 6464-6474, Vol. 25, No. 15
0022-538X/05/$08.00+0     doi:10.1128/MCB.25.15.6464-6474.2005
Copyright © 2005, American Society for Microbiology. All Rights Reserved.



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