NF-κB p50 promotes tumor cell invasion through negative regulation of invasion suppressor gene CRMP-1 in human lung adenocarcinoma cells

Lung adenocarcinoma CI1-5 cells were selected from parental CI1-0 cells based oil their high metastatic potential. In a previous Study, CRMP-1, an invasion suppressor gene was shown to be suppressed in CI1-5, cells. However, the regulation of CRMP-1 expression has not been explored. In this study, we showed nuclear factor-kappa B Controls CRMP-1 expression. The electromobility shift assay showed that while CI1-0 cells exhibited low NF-kappa B activity in response to TNF-alpha, an abundance of basal and TNF-alpha-induced NF-kappa B-DNA complex was detected in CI1-5 cells. Supershift-coupled EMSA and Western blotting of nuclear proteins, however, revealed p50 protein, but not classic p65/p50 heterodinner in the complex. ChIP and EMSA demonstrated that p50 binds to a KB site residing between -1753 and -1743 of the CRMP-1 promoter region. Transfection of antisense p50 gene into CI1-5 cells increased the CRMP-1 protein level and decreased the invasive activity of CI1-5 cells. (C) 2008 Elsevier Inc. All rights reserved.