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Impact of STAT5 on Normal Tissue Development and Cancer

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Jak-Stat Signaling : From Basics to Disease

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Abstract

STAT5A and STAT5B are two closely related transcription factors that transduce signals from cytokines and growth factors. Two tissues that rely upon STAT5 for lineage commitment and differentiation are the mammary gland and the haematopoietic system. During pregnancy, mammary epithelial cells undergo extensive proliferation and differentiation to generate milk-producing alveolar structures. Alveologenesis is abrogated in the absence of both STAT5A and B and fat pad transplantation experiments demonstrated that while the ability of stem cells to generate ductal outgrowths was not affected by loss of STAT5A/B, the alveolar compartment failed to develop in pregnant mice. In contrast, in the haematopoietic system, STAT5A and B control both stem and progenitor cell fate and are essential for the development of immune cells of the T, B and NK lineages. Aberrant STAT5 activity has major consequences and can induce tumours of both the blood and breast, in addition to other tissues. The mechanisms of constitutive STAT5 activity are manifold and include mutation of the upstream kinase JAK2.

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  1. Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge, CB2 1QP, UK

    Maria M. Caffarel & Christine J. Watson

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  1. Maria M. Caffarel
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  2. Christine J. Watson
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Correspondence to Christine J. Watson .

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  1. , Max F. Perutz Laboratories, University of Vienna, Dr. Bohr-Gasse 9/4, Vienna, 1030, Austria

    Thomas Decker

  2. , Animal Breeding and Genetics, University of Vienna, Veterinärplatz 1, Vienna, 1210, Austria

    Mathias Müller

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Caffarel, M.M., Watson, C.J. (2012). Impact of STAT5 on Normal Tissue Development and Cancer. In: Decker, T., Müller, M. (eds) Jak-Stat Signaling : From Basics to Disease. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0891-8_18

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