Moreover, in carcinogenesis experiments, tumors developed in transgenic mice carrying active Ha-ras are invasive tumors, in sharp contrast with the benign tumors originated in WT MK-2206 animals . In addition to integrin-a6 suprabasal overexpression, tumors developed in the K5-IKKa mice show reactivation of the expression of Twist. Materials and Methods Ethics Statement All experimental procedures were performed according to European and Spanish laws and regulations and approved by the our institution��s ethics committee. Approval ID: BME 3/06; BME 1/09 and BME 2�C10 by the CIEMAT Institution��s ethics commitee. Generation of Tg mice HA-tagged murine IKKa was placed under the control of a 5.2 kb 59-upstream fragment of bovine K5 promoter and a rabbit bglobin intron . Tg mice were generated by microinjection of this construct into B6D2F2 embryos using standard techniques and Tg lines were maintained by crossing with B6D2F1 mice. Mice were genotyped by PCR analysis of tail genomic DNA using primers specific for the rabbit b-globin intron. Wild type non-transgenic littermates were used as control animals. tumor cells . Maspin expression predicts a better prognosis in different types of cancers: breast , prostate , colon , oral squamous cell carcinoma , lung , larynx , malignant melanoma and ovarian cancer , although recently it has been reported that it might act as tumor promoter in colorectal or pancreatic cancers . Maspin also acts as a suppressor of metastasis in different types of cancer such as prostate, liver and breast . Interestingly, IKKa inhibits maspin expression and promotes cell metastasis in prostate cancer and hepatocarcinomas . Twist is a basic-helix-loop-helix protein known to be essential during the embryogenesis which also plays an important role as mediator of EMT during tumor progression . Twist is overexpressed in a large set of human and murine tumors including sarcomas, melanomas, gliomas and neuroblastomas being the reactivation of Twist indicative of poor prognosis. Interestingly, it has been reported that IKKa null embryos express reduced levels of Twist which suggest a positive regulation of Twist expression by IKKa. The altered expression of adhesion CPI-613 manufacturer molecules has been related to tumor development, included skin cancer, i.e., overexpression of the adhesion protein integrin-a6 in the basal layer of epidermis and hair follicles has been reported to cause malignization of skin tumors in transgenic mice . Moreover, a6b4 integrin expression in suprabasal strata serves as an early predictive marker to identify benign squamous tumors at high risk of malignant progression . In this work we have analyzed the effect of increased levels of IKKa expression in the basal layer of the epidermis of transgenic mice , and its repercussion in in vivo skin carcinogenesis.