JNK 在乳腺发育和乳腺癌中的作用。
Role of JNK in mammary gland development and breast cancer.
机构信息
Howard Hughes Medical Institute and Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
出版信息
Cancer Res. 2012 Jan 15;72(2):472-81. doi: 10.1158/0008-5472.CAN-11-1628. Epub 2011 Nov 29.
Abstract
cJun NH(2)-terminal kinase (JNK) signaling has been implicated in the developmental morphogenesis of epithelial organs. In this study, we employed a compound deletion of the murine Jnk1 and Jnk2 genes in the mammary gland to evaluate the requirement for these ubiquitously expressed genes in breast development and tumorigenesis. JNK1/2 was not required for breast epithelial cell proliferation or motility. However, JNK1/2 deficiency caused increased branching morphogenesis and defects in the clearance of lumenal epithelial cells. In the setting of breast cancer development, JNK1/2 deficiency significantly increased tumor formation. Together, these findings established that JNK signaling is required for normal mammary gland development and that it has a suppressive role in mammary tumorigenesis.
摘要
cJun NH(2)-末端激酶（JNK）信号通路参与了上皮组织器官的发育形态发生。在这项研究中，我们在乳腺中敲除了小鼠的 Jnk1 和 Jnk2 基因，以评估这些广泛表达的基因在乳腺发育和肿瘤发生中的必要性。JNK1/2 对于乳腺上皮细胞的增殖或迁移并不必需。然而，JNK1/2 的缺失导致分支形态发生增加和管腔上皮细胞清除缺陷。在乳腺癌发生的情况下，JNK1/2 的缺失显著增加了肿瘤的形成。总之，这些发现表明 JNK 信号通路对于正常乳腺发育是必需的，并且它在乳腺肿瘤发生中具有抑制作用。
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