Progression to Malignancy in the Polyoma Middle T Oncoprotein Mouse Breast Cancer Model Provides a Reliable Model for Human Diseases

Elaine Y. Lin, Joan G. Jones, Ping Li, Liyin Zhu, Kathleen D. Whitney, William J. Muller, Jeffrey W. Pollard

Research output: Contribution to journalArticle

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Abstract

Animal models are powerful tools to analyze the mechanism of the induction of human breast cancer. Here we report a detailed analysis of mammary tumor progression in one mouse model of breast cancer caused by expression of the polyoma middle T oncoprotein (PyMT) in the mammary epithelium, and its comparison to human breast tumors. In PyMT mice, four distinctly identifiable stages of tumor progression from premalignant to malignant stages occur in a single primary tumor focus and this malignant transition is followed by a high frequency of distant metastasis. These stages are comparable to human breast diseases classified as benign or in situ proliferative lesions to invasive carcinomas. In addition to the morphological similarities with human breast cancer, the expression of biomarkers in PyMT-induced tumors is also consistent with those associated with poor outcome in humans. These include a loss of estrogen and progesterone receptors as well as integrin-β1 expression and the persistent expression of ErbB2/Neu and cyclinD1 in PyMT-induced tumors as they progress to the malignant stage. An increased leukocytic infiltration was also closely associated with the malignant transition. This study demonstrates that the PyMT mouse model is an excellent one to understand the biology of tumor progression in humans.

Original languageEnglish (US)
Pages (from-to)2113-2126
Number of pages14
JournalAmerican Journal of Pathology
Volume163
Issue number5
StatePublished - Nov 2003

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Oncogene Proteins
Breast Neoplasms
Neoplasms
Breast Diseases
Progesterone Receptors
Tumor Biomarkers
Integrins
Estrogen Receptors
Breast
Epithelium
Animal Models
Neoplasm Metastasis
Carcinoma

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

Progression to Malignancy in the Polyoma Middle T Oncoprotein Mouse Breast Cancer Model Provides a Reliable Model for Human Diseases. / Lin, Elaine Y.; Jones, Joan G.; Li, Ping; Zhu, Liyin; Whitney, Kathleen D.; Muller, William J.; Pollard, Jeffrey W.

In: American Journal of Pathology, Vol. 163, No. 5, 11.2003, p. 2113-2126.

Research output: Contribution to journalArticle

Lin, Elaine Y. ; Jones, Joan G. ; Li, Ping ; Zhu, Liyin ; Whitney, Kathleen D. ; Muller, William J. ; Pollard, Jeffrey W. / Progression to Malignancy in the Polyoma Middle T Oncoprotein Mouse Breast Cancer Model Provides a Reliable Model for Human Diseases. In: American Journal of Pathology. 2003 ; Vol. 163, No. 5. pp. 2113-2126.
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