An On/Off Switch for Oncogenes

Abstract

Among the many new strategies being developed for cancer therapy are drugs that inhibit the function of oncogenes that are involved in tumorigenesis. Such drugs might be toxic if used chronically, yet they might be ineffective in the short-term because of possible reactivation of the oncogene once treatment is stopped. To investigate the latter possibility, Jain et al. (see the Perspective by Weinstein) used a sophisticated mouse genetic model to examine what happens to MYC-induced tumors when the MYC oncogene is briefly inactivated and subsequently reactivated. Surprisingly, they found that transient MYC inactivation leads to permanent loss of the neoplastic phenotype. When MYC was removed, osteogenic sarcoma cells differentiated into bone cells; reexpression of MYC did not restore the cells' tumorigenic potential but rather caused the cells to undergo apoptosis. These results suggest that brief inactivation of an oncogene may permanently change the epigenetic context of a tumor cell so that it cannot revert to its original malignant behavior. M. Jain, C. Arvanitis, K. Chu, W. Dewey, E. Leonhardt, M. Trinh, C. D. Sundberg, J. M. Bishop, D. W. Felsher, Sustained loss of a neoplastic phenotype by brief interaction of MYC. Science 296, 102-104 (2002). [Abstract] [Full Text] I. B. Weinstein, Addiction to oncogenes - the Achilles heal of cancer. Science 297, 63-64 (2002). [Summary] [Full Text]