Integrin-interacting protein Kindlin-2 induces mammary tumors in transgenic mice
Integrin-interacting protein Kindlin-2 induces mammary tumors in transgenic mice
复制标题
整合素相互作用蛋白 Kindlin-2 在转基因小鼠中诱导乳腺肿瘤
DOI：
10.1007/s11427-018-9336-6
复制
发表时间：
2019-02-01
影响因子：
9.1
通讯作者：
Zhang, Hongquan
中科院分区：
文献类型：
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作者：
Li, Bing;Chi, Xiaochun;Zhang, Hongquan
kindin -2是一种整合素相互作用蛋白，调节乳腺癌的进展。然而，目前还没有动物模型来研究kindin -2在乳腺癌变中的作用。我们利用乳腺特异性启动子乳腺肿瘤病毒（MMTV）长末端重复序列（LTR）建立了Kindlin-2转基因小鼠模型。Kindlin-2在转基因小鼠的上皮细胞中过表达。在青春期，MMTV-Kindlin-2转基因小鼠的乳腺导管树比对照小鼠生长得更快。Kindlin-2对乳腺生长有促进作用，表现为乳腺导管分支增多，管腔变大，且Kindlin-2过表达后，妊娠期乳腺内形成的肺泡增多。重要的是，kindin -2的乳腺特异性表达在平均55周龄时诱导肿瘤形成。此外，在kindlin -2诱导的乳腺肿瘤中，雌激素受体和孕酮受体水平降低，而人表皮生长因子受体2和β-catenin水平上调。这些发现表明Kindlin-2通过激活Wnt信号通路诱导乳腺肿瘤的形成。
Kindlin-2, an integrin-interacting protein, regulates breast cancer progression. However, currently, no animal model to study the role of Kindlin-2 in the carcinogenesis of mammary gland is available. We established a Kindlin-2 transgenic mouse model using a mammary gland-specific promoter, mammary tumor virus (MMTV) long terminal repeat (LTR). Kindlin-2 was overexpressed in the epithelial cells of the transgenic mice. The mammary gland ductal trees were found to grow faster in MMTV-Kindlin-2 transgenic mice than in control mice during puberty. Kindlin-2 promoted mammary gland growth as indicated by more numerous duct branches and larger lumens, and more alveoli were formed in the mammary glands during pregnancy under Kindlin-2 overexpression. Importantly, mammary gland-specific expression of Kindlin-2 induced tumor formation at the age of 55 weeks on average. Additionally, the levels of estrogen receptor and progesterone receptor were decreased, whereas human epidermal growth factor receptor 2 and β-catenin were upregulated in the Kindlin-2-induced mammary tumors. These findings demonstrated that Kindlin-2 induces mammary tumor formation via activation of the Wnt signaling pathway.