Jak2/Stat5 signaling in mammogenesis, breast cancer initiation and progression

J Mammary Gland Biol Neoplasia. 2008 Mar;13(1):93-103. doi: 10.1007/s10911-008-9062-z. Epub 2008 Jan 29.


During normal mammary gland development, the tyrosine kinase Jak2 and its main substrate, the signal transducer and activator of transcription-5 (Stat5), are critical for the growth and differentiation of alveolar progenitors as well as the survival of secretory mammary epithelial cells. Genetic studies in mouse models support a role for the Stat5 transcription factor as a proto-oncogene in mammary tumor initiation. On the other hand, the analysis of nuclear Stat5 in human breast malignancies suggests a role of the Jak2/Stat5 pathway in the restriction of the metastatic potential of neoplastic mammary epithelial cells. Following an overview on the function of the Jak2/Stat5 pathway during normal mammary gland development, this review discusses recently published observations on human breast cancers as well as experimental evidence from genetically engineered mice that propose a dual role of Jak2/Stat5 signaling in breast cancer initiation and progression. Future studies to further test the concept of contrasting effects of Jak2/Stat5 pathway on breast cancer initiation and metastatic progression are proposed.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Cell Transformation, Neoplastic / genetics
  • Cell Transformation, Neoplastic / metabolism*
  • Cell Transformation, Neoplastic / pathology*
  • Disease Progression
  • Humans
  • Janus Kinase 2 / genetics
  • Janus Kinase 2 / metabolism*
  • Proto-Oncogene Mas
  • STAT5 Transcription Factor / genetics
  • STAT5 Transcription Factor / metabolism*
  • Signal Transduction*


  • MAS1 protein, human
  • Proto-Oncogene Mas
  • STAT5 Transcription Factor
  • Janus Kinase 2