title: Redefining the expression and function of the inhibitor of differentiation 1 in mammary gland development.
abstract: The accumulation of poorly differentiated cells is a hallmark of breast neoplasia and progression. Thus an understanding of the factors controlling mammary differentiation is critical to a proper understanding of breast tumourigenesis. The Inhibitor of Differentiation 1 (Id1) protein has well documented roles in the control of mammary epithelial differentiation and proliferation in vitro and breast cancer progression in vivo. However, it has not been determined whether Id1 expression is sufficient for the inhibition of mammary epithelial differentiation or the promotion of neoplastic transformation in vivo. We now show that Id1 is not commonly expressed by the luminal mammary epithelia, as previously reported. Generation and analysis of a transgenic mouse model of Id1 overexpression in the mammary gland reveals that Id1 is insufficient for neoplastic progression in virgin animals or to prevent terminal differentiation of the luminal epithelia during pregnancy and lactation. Together, these data demonstrate that there is no luminal cell-autonomous role for Id1 in mammary epithelial cell fate determination, ductal morphogenesis and terminal differentiation.
authors.affiliation: Cancer Research Program, Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
authors.forename: Radhika
authors.initials: R
authors.lastname: Nair
authors.forename: Simon
authors.initials: S
authors.lastname: Junankar
authors.forename: Sandra
authors.initials: S
authors.lastname: O'Toole
authors.forename: Jaynish
authors.initials: J
authors.lastname: Shah
authors.forename: Alexander D
authors.initials: AD
authors.lastname: Borowsky
authors.forename: J Michael
authors.initials: JM
authors.lastname: Bishop
authors.forename: Alexander
authors.initials: A
authors.lastname: Swarbrick
mesh_terms: D000818:Animals; D002454:Cell Differentiation; D005260:Female; D018507:Gene Expression Regulation, Developmental; D051798:Inhibitor of Differentiation Protein 1 / Q000235:genetics* / Q000378:metabolism*; D007774:Lactation / Q000235:genetics / Q000378:metabolism; D008321:Mammary Glands, Animal / Q000166:cytology / Q000254:growth & development* / Q000378:metabolism* / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic; D011247:Pregnancy
chemical_list: C497455:Idb1 protein, mouse; D051798:Inhibitor of Differentiation Protein 1