Nuclear factor-kappa B-dependent expression of metastasis suppressor KAI1/CD82 gene in lung cancer cell lines expressing mutant p53

KAI1/CD82 has been shown to be a metastasis suppressor for several human ca ncers, and a recent study revealed that wild-type tumor suppressor p53 can directly activate KAI1/CD82 gene expression. However, the response of KAI1/ CD82 expression in cancer cells to exogenous stimulants has not been invest igated. The present study examined whether tumor necrosis factor (TNF), whi ch mediates many of the cellular responses associated with inflammatory rea ctions or cancer progression, can affect the KAI1/CD82 expression in lung c ancer cells and, if so, whether nuclear factor (NF)-kappaB, a key molecule in TNF-mediated gene expression, is involved in the mechanism of KAI1/CD82 induction. Our results demonstrated that expression of KAI1/CD82 in PC-14 c ells expressing mutant p53 could be augmented by TNF-alpha, and that transf er of the gene for a specific inhibitor of NF-kappaB, I kappaB alpha SR (mu tant; NF-kappaB super-repressor), into PC-14 cells could inhibit this augme ntation. The amount of NF-kappaB in the nucleus of PC-14/I kappaB alpha SR cells correlated well with KAI1/ CD82 mRNA and protein expression. In addit ion, I kappaB alpha SR gene transfer inhibited the spontaneous expression o f KAI1/CD82 protein in KAI1/CD82-high-expressing RERF-LC-OK cells, which co ntain a mutant-type p53, These observations indicate that NF-kappaB activat ion may play a role in the regulation of KAI1/CD82 expression in lung cance r cells independently of wild-type p53, and suggest that KAI1/CD82 expressi on may be regulated by interaction with the host microenvironment.