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Prognostic Significance of Nuclear Factor-B p105/p50 in Human Melanoma and Its Role in Cell Migration

Departments of ¹ Dermatology and Skin Science and ² Pathology, Jack Bell Research Centre, Vancouver Coastal Health Research Institute, University of British Columbia, Vancouver, British Columbia, Canada

Requests for reprints: Gang Li, Jack Bell Research Centre, 2660 Oak Street, Vancouver, British Columbia, Canada V6H 3Z6. Phone: 604-875-5826; Fax: 604-875-4497; E-mail: gangli{at}interchange.ubc.ca.

Transcriptional factor nuclear factor-B (NF-B) family has been shown to play an important role in tumor pathogenesis and serve as a potential target in cancer therapy. However, it is necessary to clarify the specific functions of NF-B members, which would provide the basis for the selective blockade and reduction of therapeutic side effects resulting from unspecific inhibition of NF-B members. In this study, we explored the role of NF-B p105/p50 in melanoma pathogenesis in vitro and in vivo. We found that the expression of NF-B p105/p50 significantly increased in dysplastic nevi, primary melanoma, and metastatic melanoma compared with normal nevi (P = 0.0004, ² test). Furthermore, NF-B p105/p50 nuclear staining increased with melanoma progression and strong NF-B p105/p50 nuclear staining was inversely correlated with disease-specific 5-year survival of patients with tumor thickness >2.0 mm (P = 0.014, log-rank test). Multivariate Cox regression analysis revealed that nuclear expression of NF-B p105/p50 is an independent prognostic factor in this subgroup. Moreover, we found that up-regulation of NF-B p50 enhanced melanoma cell migration, whereas small interfering RNA knockdown inhibited cell migration. In addition, overexpression of NF-B p50 induced RhoA activity and Rock-mediated formation of stress fiber in melanoma cells. Taken together, our data indicate that NF-B p105/p50 may be an important marker for human melanoma progression and prognosis as well as a potentially selective therapeutic target. (Cancer Res 2006; 66(17): 8382-8)

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