However, these mice are defective in IKK expression in both epidermis and dermis, and increasing evidences support the contribution of the tumor stroma to some of the most malignant characteristics of epithelial tumors ; therefore through this approach it is not possible to Dabrafenib discern the role that the expression of IKKa specifically in keratinocytes plays for skin carcinogenesis. A different approach to this study would be the use of conditional knockout mice lacking IKKa specifically in keratinocytes. These mice have been generated by two different groups and the skin phenotypes obtained are completely different: while one model exhibits an hyperplastic skin with absence of terminal differentiation , the other shows a nearly normal skin with terminal differentiation and no signs of hyperplasia being the reasons for this discrepancy not understood. Therefore, although skin carcinogenesis assays showing increased tumorigenesis in the IKKa conditional mice exhibiting a skin phenotype have been reported , the absence of the same experiments in the other IKKa conditional mice model casts doubts on the conclusiveness of the results. Taking into account the different results published, it seems that the role that IKKa plays in carcinogenesis could depend on the type of tumor, the cell targeted in each tumor and the strain of mice employed in the studies. Our present study supposes a different approach for study the role of IKKa in skin carcinogenesis, targeting IKKa to the basal keratinocytes of the epidermis. Our results showing the increase in the malignant potential of skin tumors developed in vivo, in transgenic mice overexpressing IKKa in keratinocytes, are in line and CUDC-907 HDAC inhibitor strengthen our previous findings showing the enhanced aggressiveness of skin tumors arising after injection of tumor epidermal cells overexpressing IKKa into nude mice . We have found that increased IKKa expression levels in the basal layer of the epidermis and ORS of the hair follicles of transgenic mice leads to alterations that originate lesions of higher malignant potential than those developed in WT mice when subjected to aberrant mitogenic stimuli. We have found that the altered expression of cyclin D1, maspin and integrin-a6 in skin of transgenic mice provide, at least in part, the molecular bases of the increase in the malignant potential of carcinomas originated in skin of K5-IKKa Tg mice.