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Jak2/Stat5 signaling in mammogenesis, breast cancer initiation and progression
1Eppley 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
Abstract:
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.
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