Sustained loss of a neoplastic phenotype by brief inactivation of MYC

被引:524
作者
Jain, M
Arvanitis, C
Chu, K
Dewey, W
Leonhardt, E
Trinh, M
Sundberg, CD
Bishop, JM
Felsher, DW [1 ]
机构
[1] Stanford Univ, Dept Med, Div Oncol, Stanford, CA 94305 USA
[2] Stanford Univ, Dept Pathol, Stanford, CA 94305 USA
[3] Univ Calif San Francisco, Dept Radiat Oncol, San Francisco, CA 94143 USA
[4] Univ Calif San Francisco, GW Hooper Fdn, San Francisco, CA 94143 USA
关键词
D O I
10.1126/science.1071489
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
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.
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页码:102 / 104
页数:4
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