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Development 129, 4159-4170 (2002)
© 2002 The Company of Biologists Limited

DEVELOPMENT AND DISEASE

Conditional loss of PTEN leads to precocious development and neoplasia in the mammary gland

Gang Li1,4, Gertraud W. Robinson2, Ralf Lesche1,*, Hilda Martinez-Diaz1, Zhaorong Jiang3, Nora Rozengurt3, Kay-Uwe Wagner2, De-Chang Wu4, Timothy F. Lane5, Xin Liu3, Lothar Hennighausen2 and Hong Wu1,{dagger}

1 Department of Molecular and Medical Pharmacology, and Howard Hughes Medical Institute,
3 Department of Pathology and Laboratory Medicine,
5 Jonsson Comprehensive Cancer Center, UCLA School of Medicine, 650 Circle Drive South, Los Angeles, CA 90095-1735, USA
2 Laboratory of Genetics and Physiology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892-0822, USA
4 Institute of Radiation Medicine, Beijing, PR China
* Present address: Epigenomics AG, Kastanienallee 24, 10435 Berlin, Germany

{dagger}Author for correspondence (e-mail: hwu{at}mednet.ucla.edu)

Accepted 4 June 2002

PTEN tumor suppressor is frequently mutated in human cancers, including breast cancers. Female patients with inherited PTEN mutations suffer from virginal hypertrophy of the breast with high risk of malignant transformation. However, the exact mechanisms of PTEN in controlling mammary gland development and tumorigenesis are unclear. In this study, we generated mice with a mammary-specific deletion of the Pten gene. Mutant mammary tissue displayed precocious lobulo-alveolar development, excessive ductal branching, delayed involution and severely reduced apoptosis. Pten null mammary epithelial cells were disregulated and hyperproliferative. Mutant females developed mammary tumors early in life. Similar phenotypes were observed in Pten-null mammary epithelia that had been transplanted into wild-type stroma, suggesting that PTEN plays an essential and cell-autonomous role in controlling the proliferation, differentiation and apoptosis of mammary epithelial cells.

Key words: PTEN, Mammary development, Cowden’s disease, Ductal growth, Apoptosis


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