Ann Thorac Surg 2006;82:248
© 2006 The Society of Thoracic Surgeons
Original article: General thoracic
Invited commentary
Robert J. Korst, MD
Weill Medical College of Cornell University, 525 East 68th St, New York, NY 10021
(Email: rjk2002{at}med.cornell.edu).
NF-
B represents a small family of protein dimers, which when activated will act as DNA transcriptional regulators. Although originally believed to exert its regulatory effects on genes involved in immunologic and inflammatory processes, it is now understood that NF-B induces the transcription of other genes, potentially involved in oncogenesis. The end result is that NF-B activation results in the inhibition of apoptotic cascades, enhances cell proliferation, and may even promote tumor angiogenesis. In addition, the development of resistance to chemotherapeutics seems to be mediated, at least in part, by activation of NF-B.
Given these specific effects of NF-B activation on DNA transcription, it is not surprising that further studies have demonstrated both increased expression and DNA binding activity of NF-B in many types of hematologic and epithelial cancers of human origin. In this regard, the current report by Zhang and colleagues [1] demonstrates that the expression of NF-B in nonsmall cell lung cancers correlates inversely with differentiation. Although no comparison with normal lung tissue is shown, NF-B levels also correlated with expression of caspase-3, cyclo-oxygenase-2, and p53 levels in these specimens. Finally, NF-B levels were an independent prognostic factor for survival in a cohort of patients resected several years earlier.
Although the role of NF-B in oncogenesis is becoming clearer, translation into the clinical arena has been more problematic. Many inhibitors of this transcription factor are currently under investigation and some are being tested in clinical trials, but no reagent possesses the desired specificity to date. Future efforts regarding NF-B and lung cancer should not only focus on experimental therapeutics, but also on corroborating the findings of Zhang and colleagues [1] in the hopes that prognostication using NF-B becomes a reality.
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- Zhang Z, Ma J, Li N, Sun N, Wang C. Expression of nuclear factor-B and its clinical significance in non-small cell lung cancer Ann Thorac Surg 2006;82:243-248.[Abstract/Free Full Text]
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