title: Human and murine prostate basal/stem cells are not direct targets of prolactin.
abstract: Local overexpression of prolactin (PRL) in the prostate of Pb-PRL transgenic mice induces benign prostate tumors exhibiting marked amplification of the epithelial basal/stem cell compartment. However, PRL-activated intracellular signaling seems to be restricted to luminal cells, suggesting that basal/stem cells may not be direct targets of PRL. Given their described role as prostate cancer-initiating cells, it is important to understand the mechanisms that regulate basal/stem cells. In this study, we evaluated whether PRL can act directly on these cells, by growing them as prostaspheres. For this, primary 3D prostasphere cultures were prepared from unfractionated cells isolated from freshly harvested human and mouse benign prostate tissues and subjected to PRL stimulation in vitro. None of the various concentrations of PRL tested showed any effects on the sizes or numbers of the prostaspheres generated. In addition, neither activation of canonical PRL-induced signaling pathways (Stat5, Stat3 or Erk1/2) nor increased expression of the proliferation marker Ki-67 were detected by immunostaining in PRL-stimulated prostaspheres. Consistent with the absence of response, PRL receptor mRNA levels were generally undetectable in mouse sphere cells. We conclude that human and mouse prostate basal/stem cells are not direct targets of PRL action. The observed amplification of basal/stem cells in Pb-PRL prostates might be due to paracrine mechanisms originating from PRL action on other cell compartments. Our current efforts are aimed at unraveling these mechanisms.
authors.affiliation: Institut Necker Enfants Malades (INEM), Inserm U1151 - CNRS UMR 8253, Equipe "Physiopathologie des hormones PRL/GH", Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, 14 rue Maria Helena Vieira da Silva - CS 61431, Bâtiment Leriche, 75993 Paris Cedex 14, France. Electronic address: lucila.sackmann-sala@inserm.fr.
authors.forename: Lucila
authors.initials: L
authors.lastname: Sackmann-Sala
authors.affiliation: Institut Necker Enfants Malades (INEM), Inserm U1151 - CNRS UMR 8253, Equipe "Physiopathologie des hormones PRL/GH", Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, 14 rue Maria Helena Vieira da Silva - CS 61431, Bâtiment Leriche, 75993 Paris Cedex 14, France; Service de Cancérologie Médicale, Hôpital Européen Georges Pompidou, Université Paris Descartes, 20 rue Leblanc, 75015 Paris, France. Electronic address: antoine.angelergues@gmail.com.
authors.forename: Antoine
authors.initials: A
authors.lastname: Angelergues
authors.affiliation: Institut Necker Enfants Malades (INEM), Inserm U1151 - CNRS UMR 8253, Equipe "Physiopathologie des hormones PRL/GH", Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, 14 rue Maria Helena Vieira da Silva - CS 61431, Bâtiment Leriche, 75993 Paris Cedex 14, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Boutillon
authors.affiliation: Service d'Urologie, Fondation Saint Jean de Dieu - Clinique Oudinot, 19 rue Oudinot, 75007 Paris, France. Electronic address: brdacrem@club-internet.fr.
authors.forename: Bruno
authors.initials: B
authors.lastname: d'Acremont
authors.affiliation: Service d'Urologie, Fondation Saint Jean de Dieu - Clinique Oudinot, 19 rue Oudinot, 75007 Paris, France. Electronic address: maidenberg@wanadoo.fr.
authors.forename: Marc
authors.initials: M
authors.lastname: Maidenberg
authors.affiliation: Service de Cancérologie Médicale, Hôpital Européen Georges Pompidou, Université Paris Descartes, 20 rue Leblanc, 75015 Paris, France. Electronic address: stephane.oudard@egp.aphp.fr.
authors.forename: Stéphane
authors.initials: S
authors.lastname: Oudard
authors.affiliation: Institut Necker Enfants Malades (INEM), Inserm U1151 - CNRS UMR 8253, Equipe "Physiopathologie des hormones PRL/GH", Université Paris Descartes, Sorbonne Paris Cité, Faculté de Médecine, 14 rue Maria Helena Vieira da Silva - CS 61431, Bâtiment Leriche, 75993 Paris Cedex 14, France. Electronic address: vincent.goffin@inserm.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Goffin
mesh_terms: D000818:Animals; D006801:Humans; D008297:Male; D051379:Mice; D011388:Prolactin / Q000378:metabolism*; D011471:Prostatic Neoplasms / Q000378:metabolism*; D011981:Receptors, Prolactin; D015398:Signal Transduction; D013234:Stem Cells / Q000378:metabolism*
chemical_list: D011981:Receptors, Prolactin; D011388:Prolactin
keywords: Basal/stem cells; Direct target; Primary cells; Prolactin; Prostaspheres; Prostate