5723

IκBα Kinase α (IKKα) has been shown to play a central role in regulation of keratinocyte terminal differentiation via a novel, independent of NF-κB signaling pathway. Ikkα-/- epidermis lacks terminal differentiation and displays a striking hyperplasia. Our preliminary data showed that immortalized Ikkα-/- keratinocytes developed into poorly differentiated spindle cell carcinomas in nude nice. To gain a better understanding of IKKα role in tumor formation and progression, we generated a transgenic mouse model, in which the human IKKα (hIKKα) is expressed in the basal and suprabasal layer cells of epidermis. Using this mouse model, we investigate the role of IKKα during mouse skin carcinogenesis by using a DMBA/TPA two-stage skin carcinogenesis protocol. The results showed that the IKKα transgenic mice developed the similar numbers of papillomas to that of wild-type mice (7.29 vs 8.28 tumor/per mouse). However, the IKKα transgenic mice significantly reduced skin carcinoma incidence (25.8% vs 50 %) and carcinoma multiplicity (0.48 vs 0.93 carcinoma/per mouse) comparing with wild type mice. In addition, the IKKα transgenic mice exhibited a delay in carcinoma incidence by 3 weeks relative to the wild-type mice (17 vs 20 weeks). These data suggest that IKKα may play an inhibitory role in malignant skin tumor progression.

[Proc Amer Assoc Cancer Res, Volume 46, 2005]