The role of ovarian hormones, age and mammary gland development in polyomavirus mammary tumorigenesis.

Polyomavirus infection of adolescent athymic female mice causes a high incidence of mammary adenocarcinomas. We have examined the role of ovarian hormones, age and mammary gland developmental stage at infection on subsequent tumor induction, viral replication and gene expression. Ovariectomy (OVX) of adolescent mice 1 week before infection decreased mammary tumor incidence and number, and significantly increased tumor incidence and number, and significantly increased tumor latency. Reduction in tumorigenesis was observed to a lesser degree if mice were OVX at the time of or after infection, indicating that ovarian hormones are mainly required for tumor initiation. Tumor incidence was also reduced with increasing age; OVX prior to infection at older ages drastically reduced tumor development. Treatment of OVX adult mice with estrogen + progesterone for 1-3 weeks prior to infection was unable to restore tumorigenesis to the level observed in intact mice. Thus, in contrast to adolescent mice, the continued presence of ovarian hormones after infection was required for maximal tumorigenesis in adult mice. The decreased tumorigenesis observed in older animals is not likely due to increased differentiation since late pregnant mice with well differentiated mammary glands remained highly susceptible to tumorigenesis. At 10 days post infection, the levels of viral genomes were moderately high and similar in all experimental groups. Early viral protein and middle T-associated kinase levels were undetectable in infected tissues in all experimental conditions. However, high levels were found in tumors, perhaps reflecting a high dosage requirement for oncogenesis.