Expression of dominant-negative ErbB2 in the mammary gland of transgenic mice reveals a role in lobuloalveolar development and lactation
Expression of dominant-negative ErbB2 in the mammary gland of transgenic mice reveals a role in lobuloalveolar development and lactation
复制标题
DOI：
10.1038/sj.onc.1202698
复制
发表时间：
1999-06-10
期刊：
影响因子：
8
通讯作者：
Stern, DF
中科院分区：
文献类型：
--
作者：
Jones, FE;Stern, DF
受体酪氨酸激酶ErbB 2/HER 2/Neu（ErbB 2）的过表达发生在15-40%的人类乳腺癌中。为了确定ErbB 2信号传导在正常小鼠乳腺发育过程中的功能，我在发育中的小鼠乳腺中表达了ErbB 2的羧基末端截短的显性负等位基因（ErbB 2 Delta IC）。尽管青春期处女和妊娠小鼠乳腺内有ErbB 2 Delta IC表达，但直到妊娠晚期才观察到表型。在产后1天，泌乳活跃，扩张的小叶肺泡未能形成。该表型在表达ErbB 2 Delta IC的经产雌性中被夸大。ErbB 2 Delta IC的免疫组织化学染色显示ErbB 2 Delta IC蛋白高水平表达与ErbB 2 Delta IC染色的小叶肺泡腔内不存在哺乳产物之间的一致性。这些结果表明，ErbB 2信号是必要的适当的乳房发育和泌乳分娩。
Overexpression of the receptor tyrosine kinase ErbB2/HER2/Neu (ErbB2) occurs in 15-40% of human breast cancers. To determine the function of ErbB2 signaling during normal mouse mammary gland development, me expressed a carboxyl-terminal truncated dominant negative allele of ErbB2 (ErbB2 Delta IC) in the developing mouse mammary gland. Despite ErbB2 Delta IC expression within mammary glands of pubescent virgin and pregnant mice, a phenotype was not observed until late in pregnancy. At 1 day post-partum, lactationally active, distended lobuloalveoli failed to form. This phenotype was exaggerated in multiparous females expressing ErbB2 Delta IC. Immunohistochemical staining for ErbB2 Delta IC revealed a concordance between high levels of ErbB2 Delta IC protein expression and the absence of lactational products within the lumens of ErbB2 Delta IC stained lobuloalveoli. These results demonstrate that ErbB2 signaling is required for proper mammary development and lactation at parturition.