The Spy1/RING0 Family Represents a Novel Mechanism Regulating Mammary Growth and Tumorigenesis

摘要

AbstractSpylA 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 SpylA 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 SpylA expression is regulated downstream of c-Myc signaling. Importantly, we show that overexpression of SpylA accelerates tumorigenesis in vivo. Collectively, this work is the first report that the Spyl/ BINGO family of proteins may play an essential role in regulating both normal and abnormal growth processes in the breast.