A novel aspartic proteinase-like gene expressed in stratified epithelia and squamous cell carcinoma of the skin.
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.
Division of Signal Transduction and Growth Control, German Cancer Research Center, Heidelberg, Germany.
Verena
V
Rhiemeier
Ute
U
Breitenbach
Karl Hartmut
KH
Richter
Christoffer
C
Gebhardt
Ingeborg
I
Vogt
Bettina
B
Hartenstein
Gerhard
G
Fürstenberger
Cornelia
C
Mauch
Jochen
J
Hess
Peter
P
Angel
D000595:Amino Acid Sequence; D000818:Animals; D016282:Aspartic Acid Endopeptidases / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000139:chemically induced / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003907:Dexamethasone / Q000494:pharmacology; D004817:Epidermis / Q000196:embryology / Q000378:metabolism; D004848:Epithelium / Q000196:embryology / Q000378:metabolism; D005260:Female; D018507:Gene Expression Regulation, Developmental; D015972:Gene Expression Regulation, Neoplastic; D016762:Genes, fos; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012867:Skin / Q000196:embryology / Q000378:metabolism* / Q000473:pathology; D012878:Skin Neoplasms / Q000139:chemically induced / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate; D018808:Transcription Factor AP-1 / Q000037:antagonists & inhibitors / Q000378:metabolism
C510448:Taps protein, mouse; D018808:Transcription Factor AP-1; D003907:Dexamethasone; D016282:Aspartic Acid Endopeptidases; D013755:Tetradecanoylphorbol Acetate