Sustained loss of a neoplastic phenotype by brief inactivation of MYC
Sustained loss of a neoplastic phenotype by brief inactivation of MYC
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DOI：
10.1126/science.1071489
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发表时间：
2002-07-05
期刊：
影响因子：
56.9
通讯作者：
Felsher, DW
中科院分区：
文献类型：
--
作者：
Jain, M;Arvanitis, C;Felsher, DW
致癌基因的药理失活作为一种可能的癌症治疗策略正在被研究。一个潜在的缺点是，停止这种治疗可能允许致癌基因的重新激活和肿瘤的再生。我们使用MYC诱导肿瘤发生的条件转基因小鼠模型来证明MYC的短暂失活导致肿瘤的持续消退和成骨肉瘤细胞向成熟骨细胞的分化。随后MYC的再激活并没有恢复细胞的恶性特性，而是诱导细胞凋亡。因此，短暂的MYC失活似乎会引起肿瘤细胞的表观遗传变化，使其对MYC诱导的肿瘤发生不敏感。这些结果提出了一种可能性，即MYC的短暂失活可能是治疗某些癌症的有效方法。
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.