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Updated: Jul 21, 2026
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Changes in Mammary Gland Morphology and Breast Cancer Risk in Rats
Published on: October 16, 2010
Ras levels and metalloproteinase activity in normal versus neoplastic rat mammary tissues
M Ballin1, A R Mackay, J L Hartzler
1Division of Cancer Etiology, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Clinical & Experimental Metastasis
|March 1, 1991
Summary
Ras oncogenes do not appear necessary for metastasis in rat mammary tumors. Studies found no direct link between ras DNA levels and cancer, nor increased metastatic capacity with ras protein induction.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Activated ras oncogenes have been linked to metastasis and type IV collagen degradation.
- N-nitrosomethylurea (NMU)-induced rat mammary carcinomas possess activated c-H-ras.
Purpose of the Study:
- To investigate the relationship between c-H-ras, metalloproteinase expression, and metastatic behavior in NMU-induced rat mammary carcinomas.
- To determine if ras amplification is essential for malignant or metastatic phenotypes.
Main Methods:
- Comparative analysis of ras DNA levels in normal rat breast tissue versus mammary carcinomas.
- Assessment of metalloproteinase expression (gelatinases) and type IV collagenolytic activity in primary tumors, metastases, and normal tissues.
- Evaluation of metastatic capacity in a v-H-ras transfected NIH/3T3 cell line upon induction of p21 ras protein synthesis.
Main Results:
- No direct correlation was found between ras DNA levels and neoplastic changes.
- No consistent differences in ras DNA levels or type IV collagenolytic activity were observed between metastatic and non-metastatic carcinomas, or between primary tumors and metastases.
- While NMU-induced mammary carcinomas showed elevated gelatinase activity, ras amplification was not required for metastasis, and induced p21 ras protein synthesis did not increase metastatic capacity in cell lines.
Conclusions:
- Ras amplification is not a prerequisite for the development of the malignant or metastatic phenotype in this rat mammary carcinoma model.
- The study challenges the direct causal link between ras oncogene activation and increased metastatic potential in this specific context.
