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Prolactin-Induced Prostate Tumorigenesis

  • Lucila Sackmann-Sala
  • Vincent Goffin
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 846)

Abstract

The physiological role of prolactin (PRL) in the prostate gland is not clearly understood. Genetically-modified mouse models that have invalidated actors of the PRL signaling axis failed to identify an essential regulatory function on this tissue. However, a large body of evidence suggests an important role for PRL in prostate tumorigenesis. Mainly through the activation of its downstream target STAT5, PRL can induce growth and survival of prostate cancer cells and tissues in several experimental settings. In the clinic, PRL expression and STAT5 activation in human prostate tumors correlate with disease severity. Available data point to a role of local (autocrine/paracrine) rather than circulating (endocrine) PRL in the induction of disease progression. In mice, transgenic expression of PRL in the prostate leads to enhanced epithelial hyperplasia and dysplasia, with amplification of basal/stem cells which have been recently identified as prostate cancer-initiating cells. Thus, targeting PRL receptor (PRLR)/STAT5 signaling may provide an alternative therapy for the treatment of prostate cancer. Corresponding targeted therapies currently in preclinical development include antagonists or blocking antibodies for the PRLR and small molecule inhibitors directed against the tyrosine kinase JAK2 upstream of STAT5. Present efforts are aimed at validating these therapies for the treatment of prostate cancer, while understanding the mechanisms of disease progression induced by PRL/STAT5.

Keywords

Prostate Cancer Androgen Receptor Benign Prostate Hyperplasia Prostate Cancer Cell Line Prostate Cancer Progression 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

The authors are grateful to Jacques-Emmanuel Guidotti for critical reading of this review and to Natascha Pigat for help in generating Fig. 10.1.

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Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Inserm U1151, Institut Necker Enfants Malades, Faculté de MédecineUniversité Paris Descartes, Sorbonne Paris CitéParisFrance

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