1. Sustained loss of a neoplastic phenotype by brief inactivation of MYC.
- Author
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Jain M, Arvanitis C, Chu K, Dewey W, Leonhardt E, Trinh M, Sundberg CD, Bishop JM, and Felsher DW
- Subjects
- Animals, Antineoplastic Agents administration & dosage, Antineoplastic Agents therapeutic use, Apoptosis, Cell Differentiation, Cell Division, Doxycycline pharmacology, Gene Expression drug effects, Mice, Mice, Transgenic, Neoplasm Transplantation, Osteocytes cytology, Osteosarcoma drug therapy, Phenotype, Transgenes, Tumor Cells, Cultured, Gene Silencing, Genes, myc, Osteosarcoma genetics, Osteosarcoma pathology
- Abstract
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.
- Published
- 2002
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