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Animal models for breast cancer
S Sukumar1, K McKenzie, Y Chen
1Molecular Biology of Breast Cancer Laboratory, Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Mutation Research
|December 1, 1995
Summary
Chemical carcinogens induce rat mammary tumors, revealing genetic events like Ha-ras oncogene activation and mutations in tumor suppressor genes during carcinogenesis. Hormonal promotion and gene amplification are key factors in tumor progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Rodent mammary tumors induced by chemical carcinogens are valuable models for studying carcinogenesis.
- N-nitroso-N-methylurea is a chemical carcinogen used to induce rat mammary carcinomas.
Purpose of the Study:
- To analyze the genetic events involved in the initiation, promotion, and progression of mammary carcinogenesis.
- To investigate the role of specific genes and mutations in rat mammary tumor development.
Main Methods:
- Induction of mammary carcinomas in rats using the chemical carcinogen N-nitroso-N-methylurea.
- Genetic analysis of mammary tumors to identify molecular alterations.
Main Results:
- The earliest observed genetic event is the activation of Ha-ras oncogenes.
- Hormonal promotion during puberty influences initiated cells.
- Tumor progression involves preferential amplification of mutated Ha-ras, PRAD-1, and IGF2.
- Loss of expression of the MK gene and mutations in the p53 tumor suppressor gene are observed.
Conclusions:
- Genetic alterations, including oncogene activation and tumor suppressor gene mutations, are critical in rat mammary carcinogenesis.
- Hormonal factors and gene amplification play significant roles in tumor progression.