Localization of large-T oncoprotein during the embryonic and fetal development of transgenic mice.

Oncoproteins are not only involved in the development of tumors but also play a role in physiological regulation in embryonic growth and differentiation. The mechanisms by which regulation is accomplished in embryonic stages differ from postnatal or adult stages. Oncoproteins responsible for tumors in the adult, i.e., products of proto-oncogenes, are prevented from causing tumors in the embryo. If oncogenes are introduced artificially into the embryo. will they be governed by the embryonic regulation described above? To answer this question we used transgenic mice in which the hybrid construct MSV-SV40-Large-T, composed of the Simian-Virus-Oncogene. Large-T with its SV40-promotor and the Moloney Murine Sarcoma Virus (MSV)-enhancer, had been integrated. Under the influence of large-T expression, these animals develop either brain or endocrine pancreas tumors. In the present investigation, we localised large-T expression during development of mouse embryos and fetuses. Interestingly, we saw large-T positive reactions in organ anlagen other than those that later develop tumors. We found large-T antigens in cartilage anlagen, e.g., in ribs and vertebrae, particularly in fetuses of days 14 to 17, and also in a variety of epithelial cells such as in the lung or the choroid plexus. Our results indicate that, as for proto-oncogene products, the effect of an artificially introduced transgenic oncogene product can also be regulated by embryonic cells.