Inhibition of anchorage-independent growth and lung metastasis of A549 lung carcinoma cells by I kappa B beta

To evaluate the role of the NF-kappaB signaling pathway in oncogenic transf ormation, we expressed I kappaB beta, a specific inhibitor of NF-kappaB, in two human lung adenocarcinoma cell lines, A549 and H441, Expression of I k appaB beta significantly reduced NF-kappaB activation induced by cotransfec tion with p65/RelA or TNF-alpha and abrogated the basal NF-kappaB activity in A549 cells. Transfection of I kappaB beta into A549, H441 and K-uas-tran sformed NIH3T3 cells suppressed anchorage-independent growth as measured by colony formation in soft agar, Anchorage-independent growth of vector-tran sfected A549 cells in reduced serum could be enhanced by both EGF and IGF-I . In contrast, only EGF but not IGF-I could induce anchorage-independent gr owth of I kappaB beta -expressing A549 cells, suggesting that the IGF-I sig naling pathway regulating growth and survival may be blocked by I kappaB be ta. Interestingly, expression of I kappaB beta suppressed growth of A549 ce lls in low serum in vitro without affecting in vivo growth subcutaneously i n nude mice, However, metastatic growth of I kappaB beta -expressing A549 c ells in the lungs of nude mice was significantly inhibited, These results p rovide evidence that NF kappaB plays an important role in anchorage-indepen dent growth and metastatic growth of lung carcinoma cells.