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(American Journal of Pathology. 2006;168:1354-1364.)
© 2006 American Society for Investigative Pathology

A Novel Aspartic Proteinase-Like Gene Expressed in Stratified Epithelia and Squamous Cell Carcinoma of the Skin

Verena Rhiemeier*, Ute Breitenbach*, Karl Hartmut Richter*, Christoffer Gebhardt*, Ingeborg Vogt*, Bettina Hartenstein*, Gerhard Fürstenberger{dagger}, Cornelia Mauch{ddagger}, Jochen Hess* and Peter Angel*

From the Division of Signal Transduction and Growth Control* and the Research Group of Eicosanoids and Epithelial Tumor Development,{dagger} German Cancer Research Center, Heidelberg, Germany; and the Department of Dermatology and Venerology,{ddagger} University of Cologne, Cologne, Germany

Homeostasis of stratified epithelia, such as the epidermis of the skin, is a sophisticated process that represents a tightly controlled balance between proliferation and differentiation. Alterations of this balance are associated with common human diseases including cancer. Here, we report the cloning of a novel cDNA sequence, from mouse back skin, that is induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and codes for a hitherto unknown aspartic proteinase-like protein (Taps). Taps represents a potential AP-1 target gene because TPA-induced expression in epidermal keratinocytes critically depends on c-Fos, and co-treatment with dexamethasone, a potent inhibitor of AP-1-mediated gene regulation, resulted in impaired activation of Taps expression. Taps mRNA and protein are restricted to stratified epithelia in mouse embryos and adult tissues, implicating a crucial role for this aspartic proteinase-like gene in differentiation and homeostasis of multilayered epithelia. During chemically induced carcinogenesis, transient elevation of Taps mRNA and protein levels was detected in benign skin tumors. However, its expression is negatively associated with dedifferentiation and malignant progression in squamous cell carcinomas of the skin. Similar expression was observed in squamous skin tumors of patients, suggesting that detection of Taps levels represents a novel strategy to discriminate the progression state of squamous skin cancers.




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Copyright © 2006 by the American Society for Investigative Pathology.