1. ¹Division of Molecular Genetics, Deutsches Krebsforschungszentrum, Heidelberg, Germany
2. ²Division of Signal Transduction and Growth Control, Deutsches Krebsforschungszentrum, Heidelberg, Germany
3. ³Division Biochemistry of Tissue-Specific Regulation, Deutsches Krebsforschungszentrum, Heidelberg, Germany
4. ⁴Department of Dermatology and Venerology, University of Cologne, Köln, Germany

Correspondence: Dr P Lichter, Division of Molecular Genetics, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 280, Heidelberg D-69120, Germany. E-mail: m.macleod@dkfz.de

⁵These authors contributed equally to this work.

Received 15 November 2004; Revised 4 July 2005; Accepted 19 July 2005; Published online 17 October 2005.

Abstract

Chemically induced mouse skin carcinogenesis represents the most extensively utilized animal model to unravel the multistage nature of tumour development and to design novel therapeutic concepts of human epithelial neoplasia. We combined this tumour model with comprehensive gene expression analysis and could identify a large set of novel tumour-associated genes that have not been associated with epithelial skin cancer development yet. Expression data of selected genes were confirmed by semiquantitative and quantitative RT-PCR as well as in situ hybridization and immunofluorescence analysis on mouse tumour sections. Enhanced expression of genes identified in our screen was also demonstrated in mouse keratinocyte cell lines that form tumours in vivo. Self-organizing map clustering was performed to identify different kinetics of gene expression and coregulation during skin cancer progression. Detailed analysis of differential expressed genes according to their functional annotation confirmed the involvement of several biological processes, such as regulation of cell cycle, apoptosis, extracellular proteolysis and cell adhesion, during skin malignancy. Finally, we detected high transcript levels of ANXA1, LCN2 and S100A8 as well as reduced levels for NDR2 protein in human skin tumour specimens demonstrating that tumour-associated genes identified in the chemically induced tumour model might be of great relevance for the understanding of human epithelial malignancies as well.