title: Profile of gene expression induced by the tumour promotor TPA in murine epithelial cells.
abstract: Malignant transformation of mouse skin by chemical carcinogens and tumour promoters, such as the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA), is a multistage process that leads to squamous cell carcinoma (SCC) formation. In an effort to identify tumour-associated genes, we studied the influence of short-term TPA-treatment on the gene expression profile of murine skin. A comprehensive microarray with some 5,000 murine gene specific cDNA fragments was established and hybridised with pooled RNA derived from control and TPA-treated dorsal skin samples. Of these genes, 54 were up- and 35 were down-regulated upon TPA application. Additionally, we performed suppression subtractive hybridisation (SSH) with respective RNA pools to generate and analyse a cDNA library enriched for TPA-inducible genes. Expression data of selected genes were confirmed by quantitative real-time PCR and Northern blot analysis. Comparison of microarray and SSH data revealed that 26% of up-regulated genes identified by expression profiling matched with those present in the SSH library. Besides numerous known genes, we identified a large set of unknown cDNAs that represent previously unrecognised TPA-regulated genes in murine skin with potential function in tumour promotion. Additionally, some TPA-induced genes, such as Sprr1A, Saa3, JunB, Il4ralpha, Gp38, RalGDS and Slpi exhibit high basal level in advanced stages of skin carcinogenesis, suggesting that at least a subgroup of the identified TPA-regulated genes may contribute to tumour progression and metastasis.
authors.affiliation: Division of Molecular Genetics, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
authors.forename: Joerg
authors.initials: J
authors.lastname: Schlingemann
authors.forename: Jochen
authors.initials: J
authors.lastname: Hess
authors.forename: Gunnar
authors.initials: G
authors.lastname: Wrobel
authors.forename: Ute
authors.initials: U
authors.lastname: Breitenbach
authors.forename: Christoffer
authors.initials: C
authors.lastname: Gebhardt
authors.forename: Peter
authors.initials: P
authors.lastname: Steinlein
authors.forename: Heidi
authors.initials: H
authors.lastname: Kramer
authors.forename: Gerhard
authors.initials: G
authors.lastname: Fürstenberger
authors.forename: Meinhard
authors.initials: M
authors.lastname: Hahn
authors.forename: Peter
authors.initials: P
authors.lastname: Angel
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
mesh_terms: D000818:Animals; D014408:Biomarkers, Tumor / Q000378:metabolism; D015152:Blotting, Northern; D002273:Carcinogens / Q000633:toxicity*; D017931:DNA Primers / Q000737:chemistry; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D015723:Gene Library; D017403:In Situ Hybridization; D015603:Keratinocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009363:Neoplasm Proteins / Q000235:genetics*; D009693:Nucleic Acid Hybridization; D016133:Polymerase Chain Reaction; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D012867:Skin / Q000187:drug effects*; D012878:Skin Neoplasms / Q000139:chemically induced / Q000235:genetics*; D013382:Subtraction Technique; D013755:Tetradecanoylphorbol Acetate / Q000633:toxicity*
chemical_list: D014408:Biomarkers, Tumor; D002273:Carcinogens; D017931:DNA Primers; D009363:Neoplasm Proteins; D012334:RNA, Neoplasm; D013755:Tetradecanoylphorbol Acetate