title: Expression of nodal and nodal receptors in prostate stem cells and prostate cancer cells: autocrine effects on cell proliferation and migration.
abstract: BACKGROUND
  Nodal, a TGFβ like growth factor, functions as an embryonic morphogen that maintains the pluripotency of embryonic stem cells. Nodal has been implicated in cancer progression; however, there is no information on expression and functions of Nodal in prostate cancer. In this study, we have investigated the expression of Nodal, its receptors, and its effects on proliferation and migration of human prostate cells.
  
  
  METHODS
  RT-PCR, qPCR, and Western blot analyses were performed to analyze expression of Nodal and Nodal receptors and its effects on phosphorylation of Smad2/3 in prostate cells. The effects on proliferation and migration were determined by (3) H-Thymidine incorporation and cell migration assays in the presence or absence of Nodal receptor inhibitor (SB431542).
  
  
  RESULTS
  Nodal was highly expressed in WPE, DU145, LNCaP, and LNCaP-C81 cells with low expression in RWPE1 and RWPE2 cells, but not in PREC, PC3 and PC3M cells. Nodal receptors are expressed at varying levels in all prostate cells. Treatment with exogenous Nodal induced phosphorylation of Smad2/3 in WPE, DU145, and PC3 cells, which was blocked by SB431542. Nodal dose-dependently inhibited proliferation of WPE, RWPE1 and DU145 cells, but not LNCaP and PC3 cells. Nodal induced cell migration in PC3 cells, which was inhibited by SB431542; Nodal had no effect on cell migration in WPE and DU145 cells. The effects of Nodal on cell proliferation and migration are mediated via ALK4 and ActRII/ActRIIB receptors and Smad 2/3 phosphorylation.
  
  
  CONCLUSIONS
  Nodal may function as an autocrine regulator of proliferation and migration of prostate cancer cells.
authors.affiliation: Center for Cancer Research and Therapeutic Development and Department of Biological Sciences, Clark Atlanta University, Atlanta, Georgia, USA.
authors.forename: BaoHan T
authors.initials: BT
authors.lastname: Vo
authors.forename: Shafiq A
authors.initials: SA
authors.lastname: Khan
mesh_terms: D030201:Activin Receptors, Type I / Q000235:genetics / Q000378:metabolism; D000704:Analysis of Variance; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D014411:Neoplastic Stem Cells / Q000378:metabolism* / Q000473:pathology; D055457:Nodal Protein / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects / Q000502:physiology; D011467:Prostate / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D011471:Prostatic Neoplasms / Q000378:metabolism* / Q000473:pathology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051899:Smad2 Protein / Q000235:genetics / Q000378:metabolism; D051900:Smad3 Protein / Q000235:genetics / Q000378:metabolism
chemical_list: D055457:Nodal Protein; D051899:Smad2 Protein; D051900:Smad3 Protein; C498932:ACVR1B protein, human; C424205:ACVR1C protein, human; D030201:Activin Receptors, Type I