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.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Cell Growth Processes / physiology
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Cell Movement / physiology
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Female
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Gene Expression
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MAP Kinase Signaling System / physiology*
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Mammary Glands, Animal / enzymology*
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Mammary Glands, Animal / growth & development*
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Mammary Neoplasms, Experimental / enzymology*
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Mammary Neoplasms, Experimental / genetics
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Mammary Neoplasms, Experimental / pathology
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Mice
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Mice, Inbred C57BL
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Mice, Nude
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Mice, Transgenic
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Mitogen-Activated Protein Kinase 8 / deficiency
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Mitogen-Activated Protein Kinase 8 / genetics
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Mitogen-Activated Protein Kinase 8 / metabolism*
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Mitogen-Activated Protein Kinase 9 / deficiency
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Mitogen-Activated Protein Kinase 9 / genetics
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Mitogen-Activated Protein Kinase 9 / metabolism*
Substances
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Mitogen-Activated Protein Kinase 9
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Mitogen-Activated Protein Kinase 8