title: The Spy1/RINGO family represents a novel mechanism regulating mammary growth and tumorigenesis.
abstract: Spy1A is a unique cell cycle activator known to mediate cell cycle progression and override the DNA damage response. This study focused on determining the role of this protein on postnatal mammary gland morphogenesis and neoplasia. Herein, we show that Spy1A levels are tightly regulated during mammary gland development and that ectopic expression stimulates precocious development and results in disrupted morphology of the gland. This follows the same trend as the oncogene c-Myc, and we show that Spy1A expression is regulated downstream of c-Myc signaling. Importantly, we show that overexpression of Spy1A accelerates tumorigenesis in vivo. Collectively, this work is the first report that the Spy1/RINGO family of proteins may play an essential role in regulating both normal and abnormal growth processes in the breast.
authors.affiliation: Department of Biological Sciences, University of Windsor-Ontario, Windsor, Ontario, Canada.
authors.forename: Azadeh
authors.initials: A
authors.lastname: Golipour
authors.forename: Dorothy
authors.initials: D
authors.lastname: Myers
authors.forename: Tiffany
authors.initials: T
authors.lastname: Seagroves
authors.forename: Daniel
authors.initials: D
authors.lastname: Murphy
authors.forename: Gerard I
authors.initials: GI
authors.lastname: Evan
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Donoghue
authors.forename: Roger A
authors.initials: RA
authors.lastname: Moorehead
authors.forename: Lisa A
authors.initials: LA
authors.lastname: Porter
mesh_terms: D000818:Animals; D002453:Cell Cycle; D018797:Cell Cycle Proteins / Q000235:genetics* / Q000502:physiology*; D004249:DNA Damage; D004847:Epithelial Cells / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D008321:Mammary Glands, Animal / Q000254:growth & development / Q000378:metabolism; D015674:Mammary Neoplasms, Animal / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008954:Models, Biological; D010957:Plasmids / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism
chemical_list: D018797:Cell Cycle Proteins; D016271:Proto-Oncogene Proteins c-myc; C529672:Spy1 protein, mouse