| First Author | Page A | Year | 2011 |
| Journal | Mol Cancer Res | Volume | 9 |
| Issue | 10 | Pages | 1329-38 |
| PubMed ID | 21821676 | Mgi Jnum | J:205219 |
| Mgi Id | MGI:5544382 | Doi | 10.1158/1541-7786.MCR-11-0168 |
| Citation | Page A, et al. (2011) IKKbeta overexpression leads to pathologic lesions in stratified epithelia and exocrine glands and to tumoral transformation of oral epithelia. Mol Cancer Res 9(10):1329-38 |
| abstractText | Alterations in nuclear factor kappaB (NFkappaB) signaling have been related with several diseases and importantly also with cancer. Different animal models with increased or diminished NFkappaB signaling have shown that NFkappaB 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 NFkappaB (IKKbeta) 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 IKKbeta overexpression in other organs and tissues. We found that elevated IKKbeta levels led to altered development and functionality of exocrine glands (i.e., mammary glands) in transgenic female mice. In oral epithelia, increased IKKbeta 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, IKKbeta also increased the malignant progression of both spontaneous and experimentally induced oral tumors. These results highlight the importance of IKKbeta in epithelial and glandular homeostasis as well as in oral tumorigenesis and open the possibility that IKKbeta activity might be implicated in the development of oral cancer in humans. |
