title: Prolactin-induced prostate tumorigenesis links sustained Stat5 signaling with the amplification of basal/stem cells and emergence of putative luminal progenitors.
abstract: Current androgen ablation therapies for prostate cancer are initially successful, but the frequent development of castration resistance urges the generation of alternative therapies and represents an important health concern. Prolactin/signal transducer and activator of transcription 5 (STAT5) signaling is emerging as a putative target for alternative treatment for prostate cancer. However, mechanistic data for its role in development or progression of prostate tumors are scarce. In vivo mouse studies found that local prolactin induced the amplification of prostate epithelial basal/stem cells. Because these cells are proposed cells of origin for prostate cancer and disease recurrence, we looked further into this amplification. Our results indicated that sustained Stat5 activation was associated with the occurrence of abnormal basal/stem cell clusters in prostate epithelium of prostate-specific prolactin-transgenic mice. Analysis of epithelial areas containing these clusters found high proliferation, Stat5 activation, and expression of stem cell antigen 1. Furthermore, enhanced prolactin signaling also led to amplification of a luminal cell population that was positive for stem cell antigen 1. These cells may originate from amplified basal/stem cells and might represent important progenitors for tumor development in prostate epithelium. These data provide a deeper understanding of the initial stages of prostate tumorigenesis induced by prolactin to help determine whether this hormone or its downstream messengers could be useful targets for prostate cancer treatment in the future.
authors.affiliation: Necker-Enfants Malades Institute (INEM), France.
authors.forename: Lucila
authors.initials: L
authors.lastname: Sackmann-Sala
authors.affiliation: Necker Institute for Sick Children, Inserm U1151 - CNRS UMR 8253, Hormone Pathophysiology Team PRL/GH, University Paris Descartes, Sorbonne Paris Cité, Faculty of Medicine, Paris, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Chiche
authors.affiliation: Necker Institute for Sick Children, Inserm U1151 - CNRS UMR 8253, Hormone Pathophysiology Team PRL/GH, University Paris Descartes, Sorbonne Paris Cité, Faculty of Medicine, Paris, France.
authors.forename: Nerea
authors.initials: N
authors.lastname: Mosquera-Garrote
authors.affiliation: Necker Institute for Sick Children, Inserm U1151 - CNRS UMR 8253, Hormone Pathophysiology Team PRL/GH, University Paris Descartes, Sorbonne Paris Cité, Faculty of Medicine, Paris, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Boutillon
authors.affiliation: Cytometry Core Facility, Inserm US 24 - CNRS UMS 3633 - SFR Necker, University Paris Descartes, Sorbonne Paris Cité, Faculty of Medicine, Paris, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Cordier
authors.affiliation: Necker Institute for Sick Children, Inserm U1151 - CNRS UMR 8253, Hormone Pathophysiology Team PRL/GH, University Paris Descartes, Sorbonne Paris Cité, Faculty of Medicine, Paris, France.
authors.forename: Ivan
authors.initials: I
authors.lastname: Pourmir
authors.affiliation: Necker Institute for Sick Children, Inserm U1151 - CNRS UMR 8253, Hormone Pathophysiology Team PRL/GH, University Paris Descartes, Sorbonne Paris Cité, Faculty of Medicine, Paris, France.
authors.forename: Luz
authors.initials: L
authors.lastname: Pascual-Mathey
authors.affiliation: Necker Institute for Sick Children, Inserm U1151 - CNRS UMR 8253, Hormone Pathophysiology Team PRL/GH, University Paris Descartes, Sorbonne Paris Cité, Faculty of Medicine, Paris, France.
authors.forename: Karima
authors.initials: K
authors.lastname: Kessal
authors.affiliation: Necker Institute for Sick Children, Inserm U1151 - CNRS UMR 8253, Hormone Pathophysiology Team PRL/GH, University Paris Descartes, Sorbonne Paris Cité, Faculty of Medicine, Paris, France.
authors.forename: Natascha
authors.initials: N
authors.lastname: Pigat
authors.affiliation: Necker Institute for Sick Children, Inserm U1151 - CNRS UMR 8253, Hormone Pathophysiology Team PRL/GH, University Paris Descartes, Sorbonne Paris Cité, Faculty of Medicine, Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Camparo
authors.affiliation: Necker Institute for Sick Children, Inserm U1151 - CNRS UMR 8253, Hormone Pathophysiology Team PRL/GH, University Paris Descartes, Sorbonne Paris Cité, Faculty of Medicine, Paris, France. Electronic address: vincent.goffin@inserm.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Goffin
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000378:metabolism* / Q000473:pathology; D002454:Cell Differentiation; D049109:Cell Proliferation; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D014411:Neoplastic Stem Cells; D011388:Prolactin / Q000235:genetics / Q000378:metabolism*; D011467:Prostate / Q000378:metabolism* / Q000473:pathology; D050799:STAT5 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*
chemical_list: D050799:STAT5 Transcription Factor; D011388:Prolactin