| First Author | Alameda JP | Year | 2011 |
| Journal | PLoS One | Volume | 6 |
| Issue | 7 | Pages | e21984 |
| PubMed ID | 21755017 | Mgi Jnum | J:174944 |
| Mgi Id | MGI:5141547 | Doi | 10.1371/journal.pone.0021984 |
| Citation | Alameda JP, et al. (2011) Increased IKKalpha expression in the basal layer of the epidermis of transgenic mice enhances the malignant potential of skin tumors. PLoS One 6(7):e21984 |
| abstractText | Non-melanoma skin cancer is the most frequent type of cancer in humans. In this study we demonstrate that elevated IKKalpha expression in murine epidermis increases the malignancy potential of skin tumors. We describe the generation of transgenic mice overexpressing IKKalpha in the basal, proliferative layer of the epidermis and in the outer root sheath of hair follicles. The epidermis of K5-IKKalpha transgenic animals shows several alterations such as hyperproliferation, mislocalized expression of integrin-alpha6 and downregulation of the tumor suppressor maspin. Treatment of the back skin of mice with the mitogenic agent 12-O-tetradecanoylphorbol-13-acetate causes in transgenic mice the appearance of different preneoplastic changes such as epidermal atypia with loss of cell polarity and altered epidermal tissue architecture, while in wild type littermates this treatment only leads to the development of benign epidermal hyperplasia. Moreover, in skin carcinogenesis assays, transgenic mice carrying active Ha-ras (K5-IKKalpha-Tg.AC mice) develop invasive tumors, instead of the benign papillomas arising in wild type-Tg-AC mice also bearing an active Ha-ras. Therefore we provide evidence for a tumor promoter role of IKKalpha in skin cancer, similarly to what occurs in other neoplasias, including hepatocarcinomas and breast, prostate and colorectal cancer. The altered expression of cyclin D1, maspin and integrin-alpha6 in skin of transgenic mice provides, at least in part, the molecular bases for the increased malignant potential found in the K5-IKKalpha skin tumors. |
