February 2017 - Vol 137 No 2

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TP63 is rarely mutated in human cancer, but the DNp63a isoform, crucial for development and maintenance of epithelia, is often increased in squamous cell carcinoma (SCC). In this issue, Devos and colleagues studied transgenic mice overexpressing DNp63a in the epidermis under control of the keratin 5 promoter (K5-DNp63atg/tg) and found that they have epidermal hyperplasia and form spontaneous cysts, among other abnormalities. Subjecting these mice to 25 weeks of topical DMBA/TPA applications known to induce papillomas in wild type (WT) mice greatly increased the yield (upper panels). In a second chemical carcinogenesis protocol, mice received DMBA alone twice weekly for 8 weeks. Compared to WT controls, DNp63atg/tg mice developed more SCCs (white arrows), and they arose more rapidly (lower panels, mice after 4 months). The authors also extensively probed the mechanisms underlying the DNp63a-driven oncogenesis. For details, see the article on page 494.