Andrechek Eran R, White Donald, Muller William J
Institute for Molecular Biology and Biotechnology, Department of Biology, McMaster University, Hamilton L8S 4K1, Canada.
Oncogene. 2005 Jan 27;24(5):932-7. doi: 10.1038/sj.onc.1208230.
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.
ErbB2受体酪氨酸激酶在正常发育和癌症中均被认为是一种关键的生长因子受体。在所有人类乳腺癌中，有20%-30%观察到该受体的扩增和过表达，且与患者生存率呈负相关。对转基因小鼠的研究表明，乳腺上皮中erbB2表达升高可直接诱发乳腺癌。尽管这些研究证实了ErbB2在乳腺癌诱发中的作用，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精确作用仍有待阐明。在此，我们证明通过Cre介导的重组对erbB2进行乳腺特异性切除会导致明显的导管伸长缺陷。除了观察到的伸长缺陷外，我们还注意到成年乳腺中的分支也减少了。尽管在未生育雌性动物的乳腺形态发生中存在这些扰动，但erbB2的靶向破坏对这些动物的泌乳能力影响很小。综上所述，这些观察结果表明erbB2在乳腺形态发生的初始阶段起着关键作用。
