Targeting janus kinase 2 in Her2/neu-expressing mammary cancer: Implications for cancer prevention and therapy.
Targeting janus kinase 2 in Her2/neu-expressing mammary cancer: Implications for cancer prevention and therapy.
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DOI：
10.1158/0008-5472.can-09-0746
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发表时间：
2009-08-15
期刊：
影响因子：
11.2
通讯作者：
Wagner KU
中科院分区：
文献类型：
--
作者：
Sakamoto K;Lin WC;Triplett AA;Wagner KU
Jak2 is essential for normal mammary gland development, but this tyrosine kinase and its main effector Stat5 are also active in a significant subset of human breast cancers. We have recently reported that Jak2 controls the expression and nuclear accumulation of Cyclin D1. Since this particular D-type cyclin has been suggested to be a key mediator for ErbB2-associated mammary tumorigenesis, we deleted Jak2 from ErbB2-expressing mammary epithelial cells prior to tumor onset and in neoplastic cells to address whether this tyrosine kinase plays a role in the initiation as well as progression of mammary cancer. Similar to Cyclin D1-deficient mice, the functional ablation of Jak2 protects against the onset of mammary tumorigenesis. In contrast, the deletion of Jak2 from neoplastic cells or the acute, ligand-inducible downregulation of this tyrosine kinase in an orthotopic transplant model did not affect the growth and survival of cancer cells. The constitutive activation of ErbB2 signaling, which is an initial event in the formation of mammary cancer, was able to override the functional role of Jak2 in regulating the expression of Akt and Cyclin D1. This might be a compensatory mechanism that explains why Jak2 is a relevant target for preventing the initiation but not the progression of ErbB2-associated mammary cancer.
