¹Department of Medicine, Division of Pulmonary and Critical Care Medicine, New York University School of Medicine, New York, NY 10016, USA

²Department of Pediatrics, New York University School of Medicine, New York, NY 10016, USA

³Department of Environmental Medicine, New York University School of Medicine, New York, NY 10016, USA

⁴Department of Microbiology, New York University School of Medicine, New York, NY 10016, USA

Correspondence to: K-M Tchou-Wong, New York University School of Medicine, 550 First Ave, MSB 147, New York, NY 10016, USA

To evaluate the role of the NF-B signaling pathway in oncogenic transformation, we expressed IB, a specific inhibitor of NF-B, in two human lung adenocarcinoma cell lines, A549 and H441. Expression of IB significantly reduced NF-B activation induced by cotransfection with p65/RelA or TNF- and abrogated the basal NF-B activity in A549 cells. Transfection of IB into A549, H441 and K-ras-transformed NIH3T3 cells suppressed anchorage-independent growth as measured by colony formation in soft agar. Anchorage-independent growth of vector-transfected 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 growth of IB-expressing A549 cells, suggesting that the IGF-I signaling pathway regulating growth and survival may be blocked by IB. Interestingly, expression of IB suppressed growth of A549 cells in low serum in vitro without affecting in vivo growth subcutaneously in nude mice. However, metastatic growth of IB-expressing A549 cells in the lungs of nude mice was significantly inhibited. These results provide evidence that NFB plays an important role in anchorage-independent growth and metastatic growth of lung carcinoma cells. Oncogene (2001) 20, 2254-2263.

IB; anchorage-independent growth; growth in low serum; apoptosis; metastasis