title: Secretogranin II is overexpressed in advanced prostate cancer and promotes the neuroendocrine differentiation of prostate cancer cells.
abstract: OBJECTIVE
  In prostate cancer (PCa), neuroendocrine differentiation (NED) is commonly observed in relapsing, hormone therapy-resistant tumours after androgen deprivation. However, the molecular mechanisms involved in the NED of PCa cells remain poorly understood. In this study, we investigated the expression of the neuroendocrine secretory protein secretogranin II (SgII) in PCa, and its potential involvement in the progression of this cancer as a granulogenic factor promoting NED.
  
  
  METHODS
  We have examined SgII immunoreactivity in 25 benign prostate hyperplasia and 32 PCa biopsies. In vitro experiments were performed to investigate the involvement of SgII in the neuroendocrine differentiation and the proliferation of PCa cell lines.
  
  
  RESULTS
  We showed that immunoreactive SgII intensity correlates with tumour grade in PCa patients. Using the androgen-dependent lymph node cancer prostate cells (LNCaP) cells, we found that NED triggered by androgen deprivation is associated with the induction of SgII expression. In addition, forced expression of SgII in LNCaP cells implemented a regulated secretory pathway by triggering the formation of secretory granule-like structures competent for hormone storage and regulated release. Finally, we found that SgII promotes prostate cancer (CaP) cell proliferation.
  
  
  CONCLUSIONS
  The present data show that SgII is highly expressed in advanced PCa and may contribute to the neuroendocrine differentiation by promoting the formation of secretory granules and the proliferation of PCa cells.
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, University of Rouen, 76821 Mont-Saint-Aignan, France; Normandy University, Normandy, France.
authors.forename: Maïté
authors.initials: M
authors.lastname: Courel
authors.affiliation: Laboratory of Neuroendocrinology and Nutritional and Climatic Environment, Faculty of Sciences Dhar-El Mahraz, University Sidi Mohamed Ben Abdellah, 30000 Fez, Morocco.
authors.forename: Fatima-Zohra
authors.initials: FZ
authors.lastname: El Yamani
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, University of Rouen, 76821 Mont-Saint-Aignan, France; Normandy University, Normandy, France.
authors.forename: David
authors.initials: D
authors.lastname: Alexandre
authors.affiliation: Department of Pathology, University Hospital Hassan II, University Sidi Mohamed Ben Abdellah, 30000 Fez, Morocco.
authors.forename: Hinde
authors.initials: H
authors.lastname: El Fatemi
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, University of Rouen, 76821 Mont-Saint-Aignan, France; Normandy University, Normandy, France.
authors.forename: Charlène
authors.initials: C
authors.lastname: Delestre
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, University of Rouen, 76821 Mont-Saint-Aignan, France; Normandy University, Normandy, France.
authors.forename: Maité
authors.initials: M
authors.lastname: Montero-Hadjadje
authors.affiliation: Department of Pathology, University Hospital Hassan II, University Sidi Mohamed Ben Abdellah, 30000 Fez, Morocco.
authors.forename: Fadl
authors.initials: F
authors.lastname: Tazi
authors.affiliation: Department of Pathology, University Hospital Hassan II, University Sidi Mohamed Ben Abdellah, 30000 Fez, Morocco.
authors.forename: Afaf
authors.initials: A
authors.lastname: Amarti
authors.affiliation: Laboratory of Neuroendocrinology and Nutritional and Climatic Environment, Faculty of Sciences Dhar-El Mahraz, University Sidi Mohamed Ben Abdellah, 30000 Fez, Morocco.
authors.forename: Rabia
authors.initials: R
authors.lastname: Magoul
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, University of Rouen, 76821 Mont-Saint-Aignan, France; Normandy University, Normandy, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Chartrel
authors.affiliation: INSERM U982, Laboratory of Neuronal and Neuroendocrine Differentiation and Communication, Institute for Research and Innovation in Biomedicine, University of Rouen, 76821 Mont-Saint-Aignan, France; Normandy University, Normandy, France. Electronic address: youssef.anouar@univ-rouen.fr.
authors.forename: Youssef
authors.initials: Y
authors.lastname: Anouar
mesh_terms: D000726:Androgen Antagonists / Q000494:pharmacology; D000728:Androgens / Q000494:pharmacology; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000378:metabolism / Q000473:pathology; D003470:Culture Media / Q000494:pharmacology; D018450:Disease Progression; D006801:Humans; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology; D017430:Prostate-Specific Antigen / Q000378:metabolism; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D053381:Secretogranin II / Q000378:metabolism*; D013256:Steroids / Q000494:pharmacology
chemical_list: D000726:Androgen Antagonists; D000728:Androgens; D003470:Culture Media; D009478:Neuropeptide Y; D053381:Secretogranin II; D013256:Steroids; D017430:Prostate-Specific Antigen
keywords: Neuroendocrine differentiation; Prostate cancer; Secretogranin; Secretory granule