期刊
MOLECULAR AND CELLULAR BIOLOGY
卷 29, 期 13, 页码 3687-3699出版社
AMER SOC MICROBIOLOGY
DOI: 10.1128/MCB.01551-08
关键词
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资金
- NIH [R01 DK52208]
- Maynard Parker Leukemia Research Fund
- William H. and Alice Goodwin
- Commonwealth Foundation for Cancer Research
- Experimental Therapeutics Center of MSKCC
Several ETS transcription factors, including ELF4/MEF, can function as oncogenes in murine cancer models and are overexpressed in human cancer. We found that Elf4/Mef activates Mdm2 expression; thus, lack of or knockdown of Elf4/Mef reduces Mdm2 levels in mouse embryonic fibroblasts (mef's), leading to enhanced p53 protein accumulation and p53-dependent senescence. Even though p53 is absent in Elf4(-/-) p53(-/-) mef's, neither oncogenic H-Ras(V12) nor c-myc can induce transformation of these cells. This appears to relate to the INK4a/ARF locus; both p19(ARF) and p16 are increased in Elf4(-/-) p53(-/-) mef's, and expression of Bmi-1 or knockdown of p16 in this context restores H-Ras(V12)-induced transformation. Thus, ELF4/MEF promotes tumorigenesis by inhibiting both the p53 and p16/Rb pathways.
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