Conditional loss of PTEN leads to precocious development and neoplasia in the mammary gland.
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.
Li
Gang
G
Department of Molecular and Medical Pharmacology, UCLA School of Medicine, 650 Circle Drive South, 90095-1735, USA.
Robinson
Gertraud W
GW
Lesche
Ralf
R
Martinez-Diaz
Hilda
H
Jiang
Zhaorong
Z
Rozengurt
Nora
N
Wagner
Kay-Uwe
KU
Wu
De-Chang
DC
Lane
Timothy F
TF
Liu
Xin
X
Hennighausen
Lothar
L
Wu
Hong
H
D000818:Animals; D001483:Base Sequence; D002471:Cell Transformation, Neoplastic; D017353:Gene Deletion; D008325:Mammary Neoplasms, Experimental / Q000209:etiology* / Q000235:genetics; D051379:Mice; D018345:Mice, Knockout; D051059:PTEN Phosphohydrolase; D010744:Phosphoric Monoester Hydrolases / Q000172:deficiency / Q000502:physiology*; D025521:Tumor Suppressor Proteins / Q000172:deficiency / Q000502:physiology*
D025521:Tumor Suppressor Proteins; D010744:Phosphoric Monoester Hydrolases; D051059:PTEN Phosphohydrolase