Lahlou Hicham, Sanguin-Gendreau Virginie, Zuo Dongmei, Cardiff Robert D, McLean Gordon W, Frame Margaret C, Muller William J
Molecular Oncology Group, McGill University, Royal Victoria Hospital, Room H5.21, 687 Pine Avenue West, Montreal, QC, Canada H3A 1A1.
Proc Natl Acad Sci U S A. 2007 Dec 18;104(51):20302-7. doi: 10.1073/pnas.0710091104. Epub 2007 Dec 3.
Elevated expression and activation of the focal adhesion kinase (FAK) occurs in a large proportion of human breast cancers. Although several studies have implicated FAK as an important signaling molecule in cell culture systems, evidence supporting a role for FAK in mammary tumor progression is lacking. To directly assess the role of FAK in this process, we have used the Cre/loxP recombination system to disrupt FAK function in the mammary epithelium of a transgenic model of breast cancer. Using this approach, we demonstrate that FAK expression is required for the transition of premalignant hyperplasias to carcinomas and their subsequent metastases. This dramatic block in tumor progression was further correlated with impaired mammary epithelial proliferation. These observations provide direct evidence that FAK plays a critical role in mammary tumor progression.
粘着斑激酶（FAK）的表达升高及激活在大部分人类乳腺癌中都有发生。尽管多项研究已表明FAK在细胞培养系统中是一种重要的信号分子，但缺乏支持FAK在乳腺肿瘤进展中发挥作用的证据。为了直接评估FAK在此过程中的作用，我们利用Cre/loxP重组系统破坏了乳腺癌转基因模型乳腺上皮中的FAK功能。通过这种方法，我们证明FAK表达对于癌前增生向癌的转变及其随后的转移是必需的。肿瘤进展中的这种显著阻滞进一步与乳腺上皮增殖受损相关。这些观察结果提供了直接证据，表明FAK在乳腺肿瘤进展中起关键作用。
