Tumor Suppressor Gene Silenced in Many Lung Cancers

DNA methylation, deacetylated histones inactivate C/EBPalpha gene rather than mutation

THURSDAY, March 16 (HealthDay News) -- A transcription factor with possible tumor suppressive functions is inactivated in a large number of lung cancers, according to a report in the March 15 issue of the Journal of the National Cancer Institute. However, the gene is modulated by methylation and other factors, rather than disrupted by a direct DNA mutation.

Christoph Plass, Ph.D., from Ohio State University in Columbus, and colleagues obtained lung cancer tissue and adjacent normal tissue from a human tissue bank to determine the state of histone acetylation and DNA methylation, common means of epigenetic regulation, around the CCAAT/enhancer-binding protein-alpha (C/EBPalpha) gene promoter.

The investigators found an increase in DNA methylation and DNA methylation complex proteins, and a decrease in acetylated histones at the C/EBPalpha promoter, both of which correlated with gene silencing in 12 of 15 lung cancer cell lines and 81 of 120 primary lung tumors. The changes appear to have occurred at the upstream promoter rather than the core promoter as previously reported.

The authors suggest that inhibitors of DNA methylation and histone deacetylases, many of which are already in clinical trials, may be effective for treatment of lung cancer. "In addition, C/EBPalpha expression should be investigated for possible use as a biomarker for early detection of lung cancer," the authors write.

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