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Science 297 (5578): 102-104

Copyright © 2002 by the American Association for the Advancement of Science

Sustained Loss of a Neoplastic Phenotype by Brief Inactivation of MYC

Meenakshi Jain,1* Constadina Arvanitis,1* Kenneth Chu,2 William Dewey,2 Edith Leonhardt,2 Maxine Trinh,2 Christopher D. Sundberg,1 J. Michael Bishop,3 Dean W. Felsher1dagger

Pharmacological inactivation of oncogenes is being investigated as a possible therapeutic strategy for cancer. One potential drawback is that cessation of such therapy may allow reactivation of the oncogene and tumor regrowth. We used a conditional transgenic mouse model for MYC-induced tumorigenesis to demonstrate that brief inactivation of MYC results in the sustained regression of tumors and the differentiation of osteogenic sarcoma cells into mature osteocytes. Subsequent reactivation of MYC did not restore the cells' malignant properties but instead induced apoptosis. Thus, brief MYC inactivation appears to cause epigenetic changes in tumor cells that render them insensitive to MYC-induced tumorigenesis. These results raise the possibility that transient inactivation of MYC may be an effective therapy for certain cancers.

1 Division of Oncology, Departments of Medicine and Pathology, Stanford University, Stanford, CA 94305-5151, USA.
2 Department of Radiation Oncology, University of California, San Francisco, CA 94143-0806, USA.
3 G. W. Hooper Foundation, University of California, San Francisco, CA 94143-0552, USA.
*   These authors contributed equally to this work.

dagger    To whom correspondence should be addressed. E-mail: dfelsher{at}

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Myc Recruits P-TEFb to Mediate the Final Step in the Transcriptional Activation of the cad Promoter.
S. R. Eberhardy and P. J. Farnham (2002)
J. Biol. Chem. 277, 40156-40162
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c-Myc is essential for vasculogenesis and angiogenesis during development and tumor progression.
T. A. Baudino, C. McKay, H. Pendeville-Samain, J. A. Nilsson, K. H. Maclean, E. L. White, A. C. Davis, J. N. Ihle, and J. L. Cleveland (2002)
Genes & Dev. 16, 2530-2543
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CANCER: Enhanced: Addiction to Oncogenes--the Achilles Heal of Cancer.
I. B. Weinstein (2002)
Science 297, 63-64
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