Role of JNK in mammary gland development and breast cancer

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Growth Processes / physiology
  • Cell Movement / physiology
  • Female
  • Gene Expression
  • MAP Kinase Signaling System / physiology*
  • Mammary Glands, Animal / enzymology*
  • Mammary Glands, Animal / growth & development*
  • Mammary Neoplasms, Experimental / enzymology*
  • Mammary Neoplasms, Experimental / genetics
  • Mammary Neoplasms, Experimental / pathology
  • Mice
  • Mice, Inbred C57BL
  • Mice, Nude
  • Mice, Transgenic
  • Mitogen-Activated Protein Kinase 8 / deficiency
  • Mitogen-Activated Protein Kinase 8 / genetics
  • Mitogen-Activated Protein Kinase 8 / metabolism*
  • Mitogen-Activated Protein Kinase 9 / deficiency
  • Mitogen-Activated Protein Kinase 9 / genetics
  • Mitogen-Activated Protein Kinase 9 / metabolism*

Substances

  • Mitogen-Activated Protein Kinase 9
  • Mitogen-Activated Protein Kinase 8