期刊
SCIENCE TRANSLATIONAL MEDICINE
卷 8, 期 350, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/scitranslmed.aad6066
关键词
-
资金
- NIH/NCI (National Cancer Institute) Project 2 grant [P50 CA90578]
- NCIS (National University Cancer Institute of Singapore) Yong Siew Yoon Research grant
- Singapore Ministry of Health's National Medical Research Council under its Singapore Translational Research (STaR) Investigator Award
- National Research Foundation of Singapore
- Singapore Ministry of Education under its Research Centres of Excellence initiative Project 3 [PO1 CA66996, 1R35CA197697]
- FAMRI (Flight Attendant Medical Research Institute) YCSA (Young Clinical Scientist Award) [052409]
- FAMRI CIA (Clinical Innovator Awards) [103063]
- FAMRI YCSA [072165]
- Doctors Cancer Foundation Award
- IASLC (International Association for the Study of Lung Cancer) Award
- MIUR (Ministry of Education, University and Research) Flagship InterOmics Project
- MSMT Navrat grant [LK21307]
- Jose Carreras fellowship [FIJC-10]
- NCI [T32/K12/R25]
- Agency for Science, Technology and Research (A*STAR), Singapore
- National Medical Research Council of Singapore [NMRC/CG/NCIS/2010]
- Dana-Farber/Harvard Cancer Center support grant [5P30 CA006516]
Lung cancer is the most common cause of cancer deaths. The expression of the transcription factor C/EBP alpha (CCAAT/enhancer binding protein a) is frequently lost in non-small cell lung cancer, but the mechanisms by which C/EBP alpha suppresses tumor formation are not fully understood. In addition, no pharmacological therapy is available to specifically target C/EBP alpha expression. We discovered a subset of pulmonary adenocarcinoma patients in whom negative/low C/EBP alpha expression and positive expression of the oncogenic protein BMI1 (B lymphoma Mo-MLV insertion region 1 homolog) have prognostic value. We also generated a lung-specific mouse model of C/EBP alpha deletion that develops lung adenocarcinomas, which are prevented by Bmi1 haploinsufficiency. BMI1 activity is required for both tumor initiation and maintenance in the C/EBP alpha-null background, and pharmacological inhibition of BMI1 exhibits antitumor effects in both murine and human adenocarcinoma lines. Overall, we show that C/EBP alpha is a tumor suppressor in lung cancer and that BMI1 is required for the oncogenic process downstream of C/EBP alpha loss. Therefore, anti-BMI1 pharmacological inhibition may offer a therapeutic benefit for lung cancer patients with low expression of C/EBP alpha and high BMI1.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据