The pattern of beta-catenin responsiveness within the mammary gland is regulated by progesterone receptor.
Experiments involving beta-catenin loss- and gain-of-function in the mammary gland have decisively demonstrated the role of this protein in normal alveologenesis. However, the relationship between hormonal and beta-catenin signaling has not been investigated. In this study, we demonstrate that activated beta-catenin rescues alveologenesis in progesterone receptor (PR; Pgr)-null mice during pregnancy. Two distinct subsets of mammary cells respond to expression of DeltaN89beta-catenin. Cells at ductal tips are inherently beta-catenin-responsive and form alveoli in the absence of PR. However, PR activity confers beta-catenin responsiveness to progenitor cells along the lateral ductal borders in the virgin gland. Once activated by beta-catenin, responding cells switch on an alveolar differentiation program that is indistinguishable from that observed in pregnancy and is curtailed by PR signaling.
Hiremath
Minoti
M
Department of Cell Biology, NYU School of Medicine, MSB 618, 550 1st Avenue, New York, NY 10016, USA.
Lydon
John P
JP
Cowin
Pamela
P
D000818:Animals; D002454:Cell Differentiation / Q000502:physiology; D005260:Female; D008297:Male; D008321:Mammary Glands, Animal / Q000166:cytology / Q000254:growth & development / Q000502:physiology; D051379:Mice; D018345:Mice, Knockout; D008894:Milk Proteins / Q000235:genetics / Q000378:metabolism; D011247:Pregnancy; D011980:Receptors, Progesterone / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D019076:Transgenes; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism*
D008894:Milk Proteins; D011980:Receptors, Progesterone; D051176:beta Catenin