Inhibition of oncogenic protein BMI1 may offer a therapeutic benefit for certain patients with lung cancer, according to the results of an analysis published in Science Translational Medicine.
In a prior study, researchers found that non-small cell lung cancer tumors expressed little of transcription factor C/EBPα, leading them to suspect that it may act as a tumor suppressant in normal cells. Therefore, they conducted a follow-up analysis investigating C/EBPα expression in a subset of patients with lung cancer who had negative or low levels of C/EBPα and a positive expression of BMI1, a protein-coding gene associated with cancer growth.
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For the study, researchers led by Elena Levantini, PhD, Dana-Farber/Harvard Cancer Center (Boston, MA), first genetically altered a line of human adenocarcinoma cells so that they overexpressed C/EBPα. Immediately, they found that increasing the expression of C/EBPα resulted in a marked reduction in BMI1 levels, supporting their initial suspicions.
They then analyzed tissue samples from 261 normal patients with non-small cell lung cancer. In those patients, they found that the same inverse relationship was true. More than 80% of tissue samples with low levels of C/EBPα were also positive for BMI1 expression. And when an analysis was conducted of tissue samples with no or low C/EBPα expression, researchers found that patients who had lower levels of BMI1 were more likely to survive. They validated their findings in mice models, where modified test subjects engineered to express no C/EBPα had higher levels of BMI1. Decreasing the expression of BMI1 inhibited the formation and growth of tumors.
From these results, researchers concluded that C/EBPα is a tumor suppressor in lung cancer and that therapeutics inhibiting BMI1 may help to improve the survival of patients with lung cancer expressing low levels of C/EBPα. These findings could be used to help design better therapies for this subset of patients.
