The Spy1/RINGO family represents a novel mechanism regulating mammary growth and tumorigenesis
The Spy1/RINGO family represents a novel mechanism regulating mammary growth and tumorigenesis
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DOI：
10.1158/0008-5472.can-07-6453
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发表时间：
2008-05-15
期刊：
影响因子：
11.2
通讯作者：
Porter, Lisa A.
中科院分区：
文献类型：
--
作者：
Golipour, Azadeh;Myers, Dorothy;Porter, Lisa A.
Spy1A 是一种独特的细胞周期激活剂，已知可以介导细胞周期进程并克服 DNA 损伤反应。这项研究的重点是确定这种蛋白质对产后乳腺形态发生和肿瘤形成的作用。在此，我们表明 Spy1A 水平在乳腺发育过程中受到严格调节，并且异位表达会刺激早熟发育并导致腺体形态破坏。这与癌基因 c-Myc 遵循相同的趋势，并且我们表明 Spy1A 表达在 c-Myc 信号传导下游受到调节。重要的是，我们发现 Spy1A 的过度表达会加速体内肿瘤的发生。总的来说，这项工作是第一份报告表明 Spy1/RINGO 蛋白家族可能在调节乳房正常和异常生长过程中发挥重要作用。
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.