Pttg1/securin is required for the branching morphogenesis of the mammary gland and suppresses mammary tumorigenesis

Proc Natl Acad Sci U S A. 2014 Jan 21;111(3):1008-13. doi: 10.1073/pnas.1318124111. Epub 2014 Jan 6.


Pituitary tumor transforming gene 1 (Pttg1) encodes the mammalian securin, which is an inhibitor of separase (a protease required for the separation of sister chromatids in mitosis and meiosis). PTTG1 is overexpressed in a number of human cancers and has been suggested to be an oncogene. However, we found that, in Pttg1-mutant females, the mammary epithelial cells showed increased proliferation and precocious branching morphogenesis. In accord with these phenotypic changes, progesterone receptor, cyclin D1, and Mmp2 were up-regulated whereas p21 (Cdkn1a) was down-regulated. These molecular changes provide explanation for the observed developmental defects, and suggest that Pttg1 is a tumor suppressor. Indeed, mice lacking Pttg1 developed spontaneous mammary tumors. Furthermore, in human breast tumors, PTTG1 protein levels were down-regulated and the reduction was significantly correlated with the tumor grade.

Publication types

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

MeSH terms

  • Animals
  • Apoptosis
  • Breast Neoplasms / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Cell Transformation, Neoplastic / genetics
  • Chromatids / chemistry
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism
  • Epithelial Cells / cytology
  • Female
  • Gene Expression Profiling
  • Gene Expression Regulation, Developmental*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Mammary Glands, Animal / growth & development
  • Mammary Glands, Animal / physiology*
  • Mammary Neoplasms, Animal / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neoplasm Proteins / metabolism
  • Securin / genetics
  • Securin / metabolism
  • Securin / physiology*
  • Time Factors


  • Cdkn1a protein, mouse
  • Cyclin-Dependent Kinase Inhibitor p21
  • Neoplasm Proteins
  • PTTG1 protein, mouse
  • Securin
  • pituitary tumor-transforming protein 1, human