Role of JNK in mammary gland development and breast cancer
Program in Molecular Medicine; Department of Cancer Biology
Animals; Cell Growth Processes; Cell Movement; Female; Gene Expression; MAP Kinase Signaling System; Mammary Glands, Animal; Mammary Neoplasms, Experimental; Mice; Mice, Inbred C57BL; Mice, Nude; Mice, Transgenic; Mitogen-Activated Protein Kinase 8; Mitogen-Activated Protein Kinase 9
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.