The Spy1/RINGO family represents a novel mechanism regulating mammary growth and tumorigenesis.
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.
Golipour
Azadeh
A
Department of Biological Sciences, University of Windsor-Ontario, Windsor, Ontario, Canada.
Myers
Dorothy
D
Seagroves
Tiffany
T
Murphy
Daniel
D
Evan
Gerard I
GI
Donoghue
Daniel J
DJ
Moorehead
Roger A
RA
Porter
Lisa A
LA
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
D018797:Cell Cycle Proteins; D016271:Proto-Oncogene Proteins c-myc; C529672:Spy1 protein, mouse