Abstract LB-46: C/EBPα acts as tumor suppressor in lung cancer by inhibiting the proto-oncogene Bmi-1.

Proceedings: AACR 104th Annual Meeting 2013; Apr 6-10, 2013; Washington, DC C/EBPα gene expression is frequently lost in non-small cell lung cancer, suggesting it acts as a tumor suppressor. Here, we generated an inducible lung-specific mouse model of C/EBPα deletion (C/EBPαLung-Δ mice) that develops lung adenocarcinomas. We observed that C/EBPα excision results in upregulation of Bmi-1, and that tumor initiation strictly depends on Bmi-1 g ene dosage, as C/EBPαLung-Δ mice carrying only one functional Bmi-1 allele escape tumorigenesis. Accordingly, C/EBPα negative human adenocarcinomas show elevated Bmi-1 expression, in line with our observation that C/EBPα acts as tumor suppressor in lung cells by directly inhibiting Bmi-1 transcription. Furthermore, pharmacological inhibition of Bmi-1 impairs the ability of C/EBPα null adenocarcinoma cells to form tumors in xenografts. Overall, we have identified Bmi-1 as a critical therapeutic target in those patients carrying abnormal C/EBPα function. Citation Format: Elena Levantini, Daniela S. Basseres, Wen Cai Zhang, Robert S. Welner, Meritxell Alberich-Jorda’, Kol Jia Yong, Bhavin M. Thakkar, Junyan Zhang, Chiara Battelli, Christopher J. Hetherington, Min Ye, Karen O'Brien, Maria Cristina Magli, Marie Loh, Min En Nga, Yin Huei Pang, Alain C. Borczuk, Lyuba Varticovski, Olivier Kocher, Pu Zhang, Ross A. Soo, Bing Lim, Balazs Halmos, Daniel G. Tenen. C/EBPα acts as tumor suppressor in lung cancer by inhibiting the proto-oncogene Bmi-1. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr LB-46. doi:10.1158/1538-7445.AM2013-LB-46