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Cytogenetic evidence for gene amplification in mouse skin carcinogenesis
Abstract:
Using our recently developed methodology for cytogenetic evaluation of solid tumors, we analyzed the occurrence of double minutes (DM) in chemically induced mouse skin carcinomas and papillomas. These studies revealed that DM were observed in 10% of the squamous cell carcinomas and in none of the papillomas screened. In addition, we analyzed four cell lines derived from mouse skin papillomas and one spontaneously transformed mouse epidermal cell line. The presence of DM was a consistent feature in all the studied cell lines. In the papilloma cell lines, the degree that DM occurred correlated with the cell line's capacity to form malignant tumors in immunosuppressed mice. DM were also observed in direct chromosomal preparations from tumors induced by one of the papilloma cell lines. Homogeneously staining regions were also present in metaphases from the spontaneously transformed cell line. We have shown here, for the first time, DM and homogeneously staining regions in mouse skin tumors and transformed cells derived from mouse skin. Since DM and homogeneously staining regions are the cytogenetic equivalents of gene amplification, which is a mechanism of increased expression of normal or altered gene products, these findings may play a relevant role in mouse epidermal carcinogenesis.
Insights
Double minutes (DM) were found in mouse skin squamous cell carcinomas, but not papillomas. DM presence in derived cell lines correlated with tumor formation, suggesting a role in mouse skin cancer development.
Area of Science:
- Cytogenetics
- Oncology
- Molecular Biology
Background:
- Double minutes (DM) and homogeneously staining regions (HSR) are cytogenetic hallmarks of gene amplification.
- Gene amplification is a key mechanism in cancer development, leading to overexpression of oncogenes.
- Understanding the presence and role of DM/HSR in carcinogenesis is crucial for developing targeted therapies.
Purpose of the Study:
- To investigate the occurrence of DM in chemically induced mouse skin tumors (carcinomas and papillomas).
- To analyze DM in mouse skin-derived cell lines, including papilloma and spontaneously transformed epidermal cell lines.
- To correlate DM presence with tumor-forming capacity and malignant transformation in mouse skin models.
Main Methods:
- Developed and applied a novel cytogenetic evaluation methodology for solid tumors.
- Analyzed DM in chemically induced mouse skin carcinomas and papillomas.
- Examined DM in five mouse skin-derived cell lines (four papilloma, one spontaneously transformed epidermal).
- Assessed tumor formation capacity of cell lines in immunosuppressed mice.
- Performed direct chromosomal preparations from induced tumors.
Main Results:
- DM were detected in 10% of squamous cell carcinomas but were absent in papillomas.
- DM were consistently present in all four mouse skin papilloma cell lines and the spontaneously transformed epidermal cell line.
- A correlation was observed between the degree of DM occurrence in papilloma cell lines and their ability to form malignant tumors.
- DM were also found in tumors directly derived from one of the papilloma cell lines.
- HSR were identified in the spontaneously transformed cell line.
Conclusions:
- This study provides the first evidence of DM and HSR in mouse skin tumors and transformed cells.
- The findings suggest that DM and HSR may play a significant role in mouse epidermal carcinogenesis.
- The correlation between DM and malignancy highlights their potential as biomarkers and therapeutic targets in skin cancer.