期刊
CANCER CELL
卷 19, 期 3, 页码 347-358出版社
CELL PRESS
DOI: 10.1016/j.ccr.2011.01.040
关键词
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资金
- Hope Funds for Cancer Research
- NIH [CA124648, CA105388, CA076905]
- CSHL Cancer Target Discovery and Development Center (CTD2) [CA148532]
- NCI CTD2 Network
We screened 124 genes that are amplified in human hepatocellular carcinoma (HCC) using a mouse hepatoblast model and identified 18 tumor-promoting genes, including CCND1 and its neighbor on 11q13.3, FGF19. Although it is widely assumed I:hat CCND1 is the main driving oncogene of this common amplicon (15% frequency in HOC), both forward-transformation assays and RNAi-mediated inhibition in human HOC cells established that FGF19 is an equally important driver gene in HCC. Furthermore, clonal growth and tumorigenicity of HCC cells harboring the 11q13.3 amplicon were selectively inhibited by RNAi-mediated knockdown of CCND1 or FGF19, as well as by an anti-FGF19 antibody. These results show that amplification could be an effective biomarker for patients most likely to respond to anti-FGF19 therapy.
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