Lung cancer is the most common cause of cancer deaths. The expression of the transcription factor C/EBPα (CCAAT/enhancer binding protein α) is frequently lost in non-small cell lung cancer, but the mechanisms by which C/EBPα suppresses tumor formation are not fully understood. In addition, no pharmacological therapy is available to specifically target C/EBPα expression. We discovered a subset of pulmonary adenocarcinoma patients in whom negative/low C/EBPα 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/EBPα deletion that develops lung adenocarcinomas, which are prevented by Bmi1 haploinsufficiency. BMI1 activity is required for both tumor initiation and maintenance in the C/EBPα-null background, and pharmacological inhibition of BMI1 exhibits antitumor effects in both murine and human adenocarcinoma lines. Overall, we show that C/EBPα is a tumor suppressor in lung cancer and that BMI1 is required for the oncogenic process downstream of C/EBPα loss. Therefore, anti-BMI1 pharmacological inhibition may offer a therapeutic benefit for lung cancer patients with low expression of C/EBPα and high BMI1.

• MeSH
• adenokarcinom plic MeSH
• adenokarcinom genetika   metabolismus   patologie   terapie   MeSH
• lidé MeSH
• mutace genetika   MeSH
• myši knockoutované MeSH
• myši MeSH
• nádory plic genetika   metabolismus   patologie   terapie   MeSH
• PRC1 genetika   metabolismus   MeSH
• protein alfa vázající zesilovač transkripce CCAAT genetika   metabolismus   MeSH
• protoonkogenní proteiny genetika   metabolismus   MeSH
• regulace genové exprese u nádorů genetika   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• BMI1 protein, human MeSH Prohlížeč
• Bmi1 protein, mouse MeSH Prohlížeč
• PRC1 MeSH
• protein alfa vázající zesilovač transkripce CCAAT MeSH
• protoonkogenní proteiny MeSH