Targeted Bmi1 inhibition impairs tumor growth in pulmonary adenocarcinomas defined by low CEBPa levels

A new subset of pulmonary NSCLC patients can be defined as negative for C/EBP alpha and positive for Bmi-1 expression, which are mimicked by our lung-specific C/EBP alpha null mice. Bmi-1 activity is required for both tumor initiation and maintenance in the C/EBP alpha null background and pharmacological inhibition of Bmi-1 exhibits anti-tumor effect. Overall, we show that C/EBP alpha is a tumor-suppressor gene in lung, and that Bmi-1 is involved in mediating the oncogenic process downstream of C/EBP alpha, implying that Bmi-1 inhibition may offer a therapeutic advantage for the subset of patients with low levels of C/EBP alpha expression. A316 cebp alpha knock out primary adenocarcinoma line cells treated with Bmi inhibition through compound PTC-209 were used for RNA extraction and hybridization on Affymetrix microarrays. We compared the microarray samples with the corresponding the control treatment (0.5% DMSO).