title: PTEN is required to maintain luminal epithelial homeostasis and integrity in the adult mammary gland.
abstract: In the mammary gland, PTEN loss in luminal and basal epithelial cells results in differentiation defects and enhanced proliferation, leading to the formation of tumors with basal epithelial characteristics. In breast cancer, PTEN loss is associated with a hormone receptor-negative, basal-like subtype that is thought to originate in a luminal epithelial cell. Here, we show that luminal-specific PTEN loss results in distinct effects on epithelial homeostasis and mammary tumor formation. Luminal PTEN loss increased proliferation of hormone receptor-negative cells, thereby decreasing the percentage of hormone receptor-positive cells. Moreover, luminal PTEN loss led to misoriented cell divisions and mislocalization of cells to the intraluminal space of mammary ducts. Despite their elevated levels of activated AKT, Pten-null intraluminal cells showed increased levels of apoptosis. One year after Pten deletion, the ducts had cleared and no palpable mammary tumors were detected. These data establish PTEN as a critical regulator of luminal epithelial homeostasis and integrity in the adult mammary gland, and further show that luminal PTEN loss alone is not sufficient to promote the progression of mammary tumorigenesis.
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA. Electronic address: amy.shore@bcm.edu.
authors.forename: Amy N
authors.initials: AN
authors.lastname: Shore
authors.affiliation: Integrative Molecular and Biomedical Sciences Graduate Program, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Chi-Hsuan
authors.initials: CH
authors.lastname: Chang
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Oh-Joon
authors.initials: OJ
authors.lastname: Kwon
authors.affiliation: The Cain Foundation Laboratories, The Jan and Dan Duncan Neurological Research Institute, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA.
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Weston
authors.affiliation: Department of Developmental Biology, University of Pittsburg, Pittsburg, PA 15213, USA.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhang
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Li
authors.initials: L
authors.lastname: Xin
authors.affiliation: Department of Molecular and Cellular Biology, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Rosen
mesh_terms: D000375:Aging / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D016764:Cell Polarity / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004847:Epithelial Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D005260:Female; D006706:Homeostasis / Q000187:drug effects; D019426:Integrases / Q000378:metabolism; D053533:Keratin-8 / Q000235:genetics; D008321:Mammary Glands, Animal / Q000187:drug effects / Q000378:metabolism*; D018345:Mice, Knockout; D051059:PTEN Phosphohydrolase / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D008941:Spindle Apparatus / Q000187:drug effects / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D013629:Tamoxifen / Q000494:pharmacology
chemical_list: D053533:Keratin-8; D011980:Receptors, Progesterone; D013629:Tamoxifen; D058570:TOR Serine-Threonine Kinases; C045073:Cre recombinase; D019426:Integrases; D051059:PTEN Phosphohydrolase
keywords: Epithelial; Homeostasis; Mammary; PTEN