Targeted disruption of ErbB2/Neu in the mammary epithelium results in impaired ductal outgrowth
Targeted disruption of ErbB2/Neu in the mammary epithelium results in impaired ductal outgrowth
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DOI：
10.1038/sj.onc.1208230
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发表时间：
2005-01-27
期刊：
影响因子：
8
通讯作者：
Muller, WJ
中科院分区：
文献类型：
--
作者：
Andrechek, ER;White, D;Muller, WJ
ErbB2 受体酪氨酸激酶被认为是正常发育和癌症中的关键生长因子受体。在 20-30% 的人类乳腺癌中观察到该受体的扩增和过度表达，并且与患者的生存率呈负相关。对转基因小鼠的研究表明，乳腺上皮中 erbB2 的表达升高可以直接诱发乳腺癌。尽管这些研究证实了 ErbB2 在乳腺癌诱导中的作用，但由于与无效突变相关的胚胎致死性，ErbB2 在正常乳腺发育中的确切作用仍有待阐明。在这里，我们证明通过 Cre 介导的重组对 erbB2 进行乳腺特异性消融会导致显着的导管伸长缺陷。除了观察到的伸长缺陷之外，我们还注意到成人乳腺的分支也减少了。尽管对处女乳腺形态发生存在这些干扰，但 erbB2 的靶向破坏对这些动物的泌乳能力几乎没有影响。总而言之，这些观察结果表明 erbB2 在乳腺形态发生的初始阶段发挥着关键作用。
The ErbB2 receptor tyrosine kinase has been implicated as a critical growth factor receptor in both normal development and cancer. Amplification and overexpression of this receptor is observed in 20-30% of all human breast cancers and is inversely correlated with patient survival. Studies with transgenic mice have established that elevated expression of erbB2 in mammary epithelium can directly induce mammary carcinomas. Although these studies confirmed a role for ErbB2 in breast cancer induction, the precise role of ErbB2 in normal mammary gland development remained to be elucidated due to the embryonic lethality associated with the null mutation. Here, we demonstrate that the mammary-specific ablation of erbB2 through Cre-mediated recombination leads to a striking ductal elongation defect. In addition to the observed elongation defect, we noted that branching in the adult mammary gland was also reduced. Despite these perturbations in virgin mammary gland morphogenesis, targeted disruption of erbB2 had little impact on the ability of these animals to lactate. Taken together, these observations indicate that erbB2 plays a critical role in the initial stages of mammary gland morphogenesis.