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Published on: April 12, 2024
Identification of novel tumour-associated genes differentially expressed in the process of squamous cell cancer
L Hummerich1, R Müller, J Hess
1Division of Molecular Genetics, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
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.
Insights
This study identifies novel genes linked to skin cancer development using a mouse model and gene expression analysis. These findings offer new insights into epithelial neoplasia and potential therapeutic targets for human skin malignancies.
Area of Science:
- Oncology
- Molecular Biology
- Dermatology
Background:
- Chemically induced mouse skin carcinogenesis is a key model for studying epithelial neoplasia.
- Understanding multistage tumor development is crucial for designing effective cancer therapies.
Purpose of the Study:
- To identify novel tumor-associated genes in skin carcinogenesis.
- To explore the role of these genes in epithelial skin cancer progression.
- To validate findings in human skin tumor specimens.
Main Methods:
- Comprehensive gene expression analysis in a chemically induced mouse skin carcinogenesis model.
- Validation of gene expression using RT-PCR, in situ hybridization, and immunofluorescence.
- Self-organizing map clustering for gene expression kinetics analysis.
- Functional annotation of differentially expressed genes.
Main Results:
- Identification of a significant set of novel tumor-associated genes in skin cancer.
- Confirmation of enhanced gene expression in mouse keratinocyte cell lines and tumor sections.
- Demonstration of involvement of cell cycle regulation, apoptosis, proteolysis, and cell adhesion in skin malignancy.
- Detection of high ANXA1, LCN2, S100A8 transcript levels and reduced NDR2 protein in human skin tumors.
Conclusions:
- Novel genes identified in the mouse model are relevant to human epithelial malignancies.
- The findings provide a foundation for understanding skin cancer development and identifying therapeutic strategies.
- The study highlights the translational potential of the mouse skin carcinogenesis model for human cancer research.
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