SV40 T-ANTIGEN INDUCES BREAST-CANCER FORMATION WITH A HIGH-EFFICIENCYIN LACTATING AND VIRGIN WAP-SV-T TRANSGENIC ANIMALS BUT WITH A LOW EFFICIENCY IN OVARIECTOMIZED ANIMALS

The whey acid protein (WAP) is a major mouse milk protein and its gene expression is induced by various lactotrophic hormones leg, estrogen, progesterone). Transgenic animals harboring the early SV40 coding reg ion (T/t-antigen) under the transcriptional control of the WAP promote r develop breast cancer after the first lactation period. The tumor ce lls synthesize the SV40 T-antigen with a high efficiency indicating th at WAP-SV-T expression escapes down-regulation after the lactation per iod. However about 5-10% of the tumors became T-antigen negative durin g tumor progession and WAP-SV-T expression was only demonstrable by PC R analysis. Both T-antigen positive and negative tumor cells expressed the estrogen and progesterone receptor at a comparable rate, indicati ng that hormone receptor levels do not determine expression of the WAP -SV-T transgene, Furthermore, WAP and WAP-SV-T gene expression are not restricted to the pregnancy-lactation period. Virgin animals also exp ress both genes with a low efficiency and about 70% of these animals a lso developed T-antigen positive breast tumors, The tumor rate however was strongly reduced in ovariectomized animals, indicating that the o vary hormones play a critical role in breast cancer formation.