IKKβ Overexpression Leads to Pathologic Lesions in Stratified Epithelia and Exocrine Glands and to Tumoral Transformation of Oral Epithelia

Alterations in nuclear factor kappaB (NF kappa B) signaling have been related with several diseases and importantly also with cancer. Different animal models with increased or diminished NF kappa B signaling have shown that NF kappa B subunits and their regulators are relevant to the pathophysiology of different organs and tissues. In particular, both the deletion of the regulatory subunit beta of the kinase of the inhibitor of NF kappa B (IKK beta) and its overexpression in epidermis lead to the development of skin inflammatory diseases not associated with tumoral lesions. In this work, we have studied the consequences of IKK beta overexpression in other organs and tissues. We found that elevated IKK beta levels led to altered development and functionality of exocrine glands (i.e., mammary glands) in transgenic female mice. In oral epithelia, increased IKK beta expression produced lichenoid inflammation with abundant granulocytes, macrophages, and B cells, among other inflammatory cells. This inflammatory phenotype was associated with high incidence of tumoral lesions in oral epithelia, contrary to what was found in skin. Moreover, IKK beta also increased the malignant progression of both spontaneous and experimentally induced oral tumors. These results highlight the importance of IKK beta in epithelial and glandular homeostasis as well as in oral tumorigenesis and open the possibility that IKK beta activity might be implicated in the development of oral cancer in humans. Mol Cancer Res; 9(10); 1329-38. (C) 2011 AACR.