Department of Cancer and Cell Biology, University of Cincinnati College of Medicine, OH 45267, USA.
Cancer Lett. 2010 Oct 28;296(2):186-93. doi: 10.1016/j.canlet.2010.04.011.
The CHEK2 (Chk2 in mice) polymorphic variant, CHEK21100delC, leads to genomic instability and is associated with an increased risk for breast cancer. The Ron receptor tyrosine kinase is overexpressed in a large fraction of human breast cancers. Here, we asked whether the low penetrance Chk21100delC allele alters the tumorigenic efficacy of Ron in the development of mammary tumors in a mouse model. Our data demonstrate that Ron overexpression on a Chk2*1100delC background accelerates the development of mammary tumors, and shows that pathways mediated by a tyrosine kinase receptor and a regulator of the cell cycle can act to hasten tumorigenesis in vivo.
CHEK2（小鼠中的 Chk2）多态性变体 CHEK21100delC 导致基因组不稳定，并与乳腺癌风险增加相关。Ron 受体酪氨酸激酶在很大一部分人类乳腺癌中过表达。在这里，我们想知道低外显度的 Chk21100delC 等位基因是否会改变 Ron 在小鼠模型中乳腺肿瘤发生发展中的致瘤效力。我们的数据表明，在 Chk2*1100delC 背景下 Ron 的过表达加速了乳腺肿瘤的发展，并表明由酪氨酸激酶受体和细胞周期调节剂介导的途径可以在体内加速肿瘤发生。
