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Identification of novel tumour-associated genes differentially expressed in the process of squamous cell cancer development

Oncogene volume 25, pages 111–121 (2006)Cite this article

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.

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Abbreviations

BCC:

basal cell carcinoma

DMBA:

7,12-dimethylbenz-[α]-anthracene

ISH:

in situ hybridization

NIA:

National Institute of Aging

NS:

normal skin

PAP:

papilloma

RQ-PCR:

real-time quantitative reverse transcription PCR

RT-PCR:

reverse transcription PCR

SCC:

squamous cell carcinoma

SOM:

self-organizing maps

TPA:

12-O-tetradecanoylphorbol-13-acetate

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Acknowledgements

We thank Gunnar Wrobel, Bjoern Tews and Grischa Toedt for statistical and IT support as well as Ingeborg Vogt, Inga Ruiner, Heidi Kramer and Daniela Bodemer for technical assistance. This study was supported by the German Ministry for Education and Research (National Genome Research Network, NGFN-1, 01 GR 0101, NGFN-2, 01 GS 0460) to PL and MH, the Deutsche Forschungsgemeinschaft (AN 182/8-2), by the Research Training Network (RTN) Program of the European Community to PA and the Centre of Molecular Medicine, University of Cologne (BMFT/IDZ 10, Grant 01 GB 950/4) to CM.

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Author notes

  1. L Hummerich and R Müller: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Molecular Genetics, Deutsches Krebsforschungszentrum, Heidelberg, Germany

    L Hummerich, F Kokocinski, M Hahn & P Lichter

  2. Division of Signal Transduction and Growth Control, Deutsches Krebsforschungszentrum, Heidelberg, Germany

    R Müller, J Hess & P Angel

  3. Division Biochemistry of Tissue-Specific Regulation, Deutsches Krebsforschungszentrum, Heidelberg, Germany

    G Fürstenberger

  4. Department of Dermatology and Venerology, University of Cologne, Köln, Germany

    C Mauch

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  1. L Hummerich
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Correspondence to P Lichter.

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Hummerich, L., Müller, R., Hess, J. et al. Identification of novel tumour-associated genes differentially expressed in the process of squamous cell cancer development. Oncogene 25, 111–121 (2006). https://doi.org/10.1038/sj.onc.1209016

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