Transgenic Polyoma middle-T mice model premalignant mammary disease

Cancer Res. 2001 Nov 15;61(22):8298-305.

Abstract

Mice transgenic for the Polyomavirus middle T (PyV-mT) gene have been widely used to study mammary tumorigenesis and metastasis. Although numerous molecular insights were gained from the analysis of these transgenic malignant tumors, the early events leading to malignant transformation have not been systematically investigated nor has the biological potential of hyperplastic lesions been documented. This paper presents the first comprehensive histopathological characterization of transgenic PyV-mT hyperplasias together with classical transplantation experiments designed to test the growth potential of these lesions. Moreover, stable hyperplastic outgrowth lines were established as a tool to study premalignant PyV-mT-induced hyperplasias in detail. Each line has a different tumor latency, indicating that PyV-mT-induced hyperplasias, like early proliferative lesions seen in the human breast, are heterogeneous with respect to their malignant potential. Our results settle a controversy; they establish that PyV-mT gene expression alone is insufficient to induce tumors and that additional events are required for tumorigenesis and metastasis. These results support the use of PyV-mT transgenic mice as a model for investigating the multistep progression of malignant mammary tumorigenesis and metastasis.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Polyomavirus Transforming / biosynthesis
  • Antigens, Polyomavirus Transforming / genetics*
  • Cell Division / physiology
  • Disease Models, Animal
  • Female
  • Gene Expression
  • Mammary Neoplasms, Experimental / blood supply
  • Mammary Neoplasms, Experimental / genetics*
  • Mammary Neoplasms, Experimental / metabolism
  • Mammary Neoplasms, Experimental / pathology*
  • Mammary Tumor Virus, Mouse / genetics
  • Mice
  • Mice, Transgenic
  • Neoplasm Transplantation
  • Precancerous Conditions / blood supply
  • Precancerous Conditions / genetics*
  • Precancerous Conditions / metabolism
  • Precancerous Conditions / pathology*
  • Receptors, Estrogen / biosynthesis
  • Receptors, Progesterone / biosynthesis
  • Tumor Suppressor Protein p53 / biosynthesis

Substances

  • Antigens, Polyomavirus Transforming
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Tumor Suppressor Protein p53