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Sustained Loss of a Neoplastic Phenotype by Brief Inactivation of MYC

2002; American Association for the Advancement of Science; Volume: 297; Issue: 5578 Linguagem: Inglês

10.1126/science.1071489

1095-9203

Meenakshi Jain, Constadina Arvanitis, Kenneth C. Chu, William C. Dewey, Edith A. Leonhardt, Maxine Trinh, Christopher Sundberg, J. Michael Bishop, Dean W. Felsher,

Acute Myeloid Leukemia Research

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.