title: Neuronal Trans-Differentiation in Prostate Cancer Cells.
abstract: Neuroendocrine (NE) differentiation in prostate cancer (PCa) is an aggressive phenotype associated with therapy resistance. The complete phenotype of these cells is poorly understood. Clinical classification is based predominantly on the expression of standard NE markers.
  
  
  
  We analyzed the phenotype of NE carcinoma of the prostate utilizing in vitro methods, in silico, and immunohistochemical analyses of human disease.
  
  
  
  LNCaP cells, subjected to a variety of stressors (0.1% [v/v] fetal bovine serum, cyclic AMP) induced a reproducible phenotype consistent with neuronal trans-differentiation. Cells developed long cytoplasmic processes resembling neurons. As expected, serum deprived cells had decreased expression in androgen receptor and prostate specific antigen. A significant increase in neuronal markers also was observed. Gene array analysis demonstrated that LNCaP cells subjected to low serum or cAMP showed statistically significant manifestation of a human brain gene expression signature. In an in silico experiment using human data, we identified that only hormone resistant metastatic prostate cancer showed enrichment of the "brain profile." Gene ontology analysis demonstrated categories involved in neuronal differentiation. Three neuronal markers were validated in a large human tissue cohort.
  
  
  
  This study proposes that the later stages of PCa evolution involves neuronal trans-differentiation, which would enable PCa cells to acquire independence from the neural axis, critical in primary tumors. Prostate 76:1312-1325, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Division of Radiation Oncology, Department of Radiology, Baylor College of Medicine, Houston, Texas.
authors.forename: Andrew
authors.initials: A
authors.lastname: Farach
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Yi
authors.initials: Y
authors.lastname: Ding
authors.affiliation: Center for Clinical and Translational Sciences, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: MinJae
authors.initials: M
authors.lastname: Lee
authors.affiliation: Department of Medicine, Baylor College of Medicine, Houston, Texas.
authors.forename: Chad
authors.initials: C
authors.lastname: Creighton
authors.affiliation: Department of Biochemistry and Cell Biology, MS-140, Rice University, Houston, Texas.
authors.forename: Nikki A
authors.initials: NA
authors.lastname: Delk
authors.affiliation: Department of Pathology, Baylor College of Medicine, Houston, Texas.
authors.forename: Michael
authors.initials: M
authors.lastname: Ittmann
authors.affiliation: Department of Urology, Houston Methodist Hospital, Houston, Texas.
authors.forename: Brian
authors.initials: B
authors.lastname: Miles
authors.affiliation: Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, Texas.
authors.forename: David
authors.initials: D
authors.lastname: Rowley
authors.affiliation: Department of Biochemistry and Cell Biology, MS-140, Rice University, Houston, Texas.|Department of Molecular and Cell Biology, Baylor College of Medicine, Houston, Texas.
authors.forename: Mary C
authors.initials: MC
authors.lastname: Farach-Carson
authors.affiliation: Department of Pathology and Laboratory Medicine, University of Texas Health Science Center at Houston, Houston, Texas.
authors.forename: Gustavo E
authors.initials: GE
authors.lastname: Ayala
mesh_terms: D018278:Carcinoma, Neuroendocrine / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D054338:Cell Transdifferentiation / Q000502:physiology*; D006801:Humans; D008297:Male; D009474:Neurons / Q000378:metabolism / Q000473:pathology*; D017430:Prostate-Specific Antigen / Q000096:biosynthesis / Q000235:genetics; D011471:Prostatic Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011944:Receptors, Androgen / Q000096:biosynthesis / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: C410798:AR protein, human; D011944:Receptors, Androgen; D017430:Prostate-Specific Antigen
keywords: nerves; neuroendocrine; neuronal trans-differentiation; neurons; prostate cancer; resistance phenotype; small cell