Jak2/Stat5 signaling in mammogenesis, breast cancer initiation and progression.
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.
Wagner
Kay-Uwe
KU
Eppley Institute for Research in Cancer and Allied Diseases, Department of Pathology and Microbiology, University of Nebraska Medical Center, Omaha, NE 68198, USA. kuwagner@unmc.edu
Rui
Hallgeir
H
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D050799:STAT5 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction
C000715470:MAS1 protein, human; D000090063:Proto-Oncogene Mas; D050799:STAT5 Transcription Factor; D053614:Janus Kinase 2