International Mammalian Genome Society

17th International Mouse Genome Conference

9-12 November 2003, Braunschweig, Germany


Hummerich L
Division of Molecular Genetics

Co-Authors: 2) Müller R, 1) Wrobel G, 1) Kokocinski F, 2) Gack S, 2) Schorpp-Kistner M, 3) Fürstenberger G, 2) Hess J, 1) Hahn M, 2) Angel P, 1) Lichter P
Institutions: 1) Division of Molecular Genetics, 2) Division of Signal Transduction and Growth Control, 3) Division Biochemistry of Tissue-Specific Regulation, Deutsches Krebsforschungs-zentrum, Im Neuenheimer Feld 280, D-69120 Heidelberg, Germany

The mouse skin models of chemical carcinogenesis have been extensively used to investigate skin tumour initiation and promotion and the conversion of benign tumours (papillomas) to malignant squamous cell carcinomas (SCC). To provide reliable diagnostic markers and to develop novel therapeutic targets for cancer prevention and treatment, an understanding of the molecular basis of tumourigenesis will be essential. Particularly, identification and functional characterization of cellular genes that are targeted by oncogenic stimuli represents an auspicious experimental approach. For the studies of skin cancer modulation 7,12-dimethylbenzanthracene (DMBA)-initiated and 12-O-tetradecanoyl-phorbol-13-acetate (TPA)-promoted back skin of mice are used to identify tumour-associated genes in the steps of initiation, promotion and progression. The different RNA samples derived from control and short-term TPA-treated skin, papilloma and SCC biopsies were hybridised on two different arrays comprising 20K (LION arrayTAG™) and 15K (National Institute of Aging) murine gene specific cDNA fragments. Expression data of selected genes were confirmed by semiquantitative RT-PCR, quantitative real-time PCR (RQ-PCR) and in situ hybridisation (ISH). Besides numerous known genes, we identified a large set of unknown cDNAs representing previously unrecognised TPA-regulated genes in murine skin with potential function in tumour promotion. The detailed analysis of genes, involved in the development of papillomas and in the conversion of papillomas to malignant squamous cell carcinomas, might identify potential candidates for a better understanding of the molecular mechanism of skin carcinogenesis.

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