Characterization of the mammary hyperplasia, dysplasia and neoplasia induced in athymic female adult mice by polyomavirus.
We have characterized mammary oncogenesis induced after polyomavirus infection of adult female nude mice regarding histopathogenesis, viral replication and viral and cellular oncogene expression. A unique transient generalized epithelial hyperplasia was observed (starting at 2 weeks post infection), preceding the development of dysplasias (onset 6 weeks post infection) and multiple neoplasias (onset 6 weeks post infection) in all glands. The ductal epithelium was the target for neoplastic transformation, and the occurrence of numerous ductal dysplasias coincided with the appearance of frank tumors. Stromal abnormalities were also seen. Tumor growth was not dependent upon ovarian hormones, and new tumors continued to develop in ovariectomized mice. Viral replication, high although variable, preceded but did not correlate with oncogenesis. Most but not all tumors contained high levels of unintegrated viral DNA. Tumors produced very low levels of live virus. Viral gene expression was markedly increased in the tumors compared with the infected but morphologically normal glands. The expression of c-myc was moderately increased (fourfold); changes in c-int-2 and c-Ha-ras expression were slight and inconsistent, while expression of c-neu and c-int-1 was unchanged.
Haslam
S Z
SZ
Department of Physiology, Michigan State University, East Lansing 48824-1101.
Wirth
J J
JJ
Counterman
L J
LJ
Fluck
M M
MM
D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D015967:Gene Expression Regulation, Viral; D006965:Hyperplasia; D008321:Mammary Glands, Animal / Q000382:microbiology / Q000473:pathology; D008325:Mammary Neoplasms, Experimental / Q000235:genetics / Q000382:microbiology / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009376:Neoplasms, Hormone-Dependent / Q000382:microbiology; D011120:Polyomavirus; D011519:Proto-Oncogenes / Q000235:genetics; D014412:Tumor Virus Infections / Q000235:genetics / Q000473:pathology*; D015854:Up-Regulation; D014779:Virus Replication