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Expression of the Retrotransposons, Intracisternal A-Particles, during Neoplastic Progression of Mouse Mammary Epithelium Analyzed with a Monoclonal Antibody¹

Department of Experimental Pathology, Roswell Park Memorial Institute, Buffalo, New York 14263-0001

In order to develop new probes for investigating cellular alterations accompanying neoplastic progression of mouse mammary epithelium, rat monoclonal antibodies were prepared against cytoskeletal extracts of cultured normal and malignant mouse mammary epithelial cells. One of these antibodies, VG10, reacted in immunofluorescent staining with the majority of mouse mammary epithelial cells from hyperplastic alveolar nodule outgrowth lines of hormonal, chemical, and viral etiologies and the primary adenocarcinomas arising spontaneously from the nodules. Moreover, most mammary carcinomas developing in BALB/cfC3H, BALB/cV, and 7,12-dimethylbenzanthracene-treated BALB/c mice also had cells recognized by VG10. In contrast, normal mouse mammary epithelial cells from virgin and pregnant mice were unreactive. Immunoelectron microscopy identified the reactive component in the abnormal cells as intracisternal A-particles (IAPs), endogenous retrovirions with the ability to transpose in the mouse genome. Western blotting experiments established that the VG10 antibody is specific for the M_r 73,000 gag protein of IAPs. The results indicate that expression of IAPs is a common occurrence in the evolution of malignancy in mammary epithelium of BALB/c mice and may be induced during the transformation of normal cells to the preneoplastic stage. Expression of IAPs is therefore a candidate marker for a step in neoplastic progression in this system and has the potential for contributing to the carcinogenic process.

¹ Supported by Grant CA32937 from the National Cancer Institute.

² To whom requests for reprints should be addressed.

Received 9/11/89. Revised 12/21/89.