Cell-Matrix Interactions in Breast Carcinoma Invasion.
Annual rept. 15 Dec 94-14 Dec 95,
NEW YORK UNIV MEDICAL CENTER NY
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We have used a transgenic mouse model system to investigate the role of integrin defects in breast cancer progression. Transgenic mice carrying an activated form of the N-ras oncogene under the control of the Mammary Tumor Virus Long Terminal Repeat promoter develop mammary carcinomas with a high frequency during the first few months of their life. The a6p4 and, to a minor extent, the a2b1 integrin were found to be upregulated and diffusely distributed at the tumor cell surface in the primary lesions of these mice. These events were accompanied by a loss of laminin staining indicative of defective basement membrane deposition. The a3 bl integrin was diffusely distributed, but not upregulated. Since transfection of N-ras into cultured murine breast epithelial cells did not produce the changes in integrin expression detected in vivo, it is likely that these changes occur as a result of tumor progression independently of a direct action of N-ras. The above described studies indicate that the expression, and possibly the function, of several integrins involved in adhesion to the basement membrane is altered during the in vivo progression of breast cancer in the N-ras transgenic mouse model.
- Medicine and Medical Research
- Genetic Engineering and Molecular Biology