title: Function of mutant and wild-type plexinb1 in prostate cancer cells.
abstract: BACKGROUND
  Semaphorins act as chemotactic cues for cell movement via their transmembrane receptors, plexins. Somatic missense mutations in the plexinB1 gene coupled with overexpression of the protein frequently occur in prostate tumors, indicating a role for plexinB1 in the pathogenesis of prostate cancer. However, the effect of semaphorin/plexin signaling is highly context dependent and whether plexinB1 acts as an inducer or inhibitor of prostate tumor progression in this context is not known.
  
  
  METHODS
  The response of prostate cancer cell lines to plexinB1 activation was assessed in migration, invasion, proliferation and protein phosphorylation assays. Expression was assessed by quantitative RTPCR and immunoblotting.
  
  
  RESULTS
  Different prostate cancer cell lines respond to Sema4D (the ligand for plexinB1) in diverse ways. Activation of endogenous plexinB1 enhances migration, invasion and anchorage-independent growth of LNCaP prostate cancer cells via activation of ErbB2 and Akt. In contrast, Sema4D-stimulation decreased the motility and proliferative capacity of PC3 cells. LNCaP has a missense mutation (Thr1697Ala) in the plexinB1 gene while LNCaP-LN3, a derivative of LNCaP, expresses high levels of wild-type plexinB1 only. Sema4D stimulation increases the motility and anchorage independent growth of both cell lines, showing that these responses are not dependent on the presence of the Thr1697Ala form of plexinB1. ErbB2 and plexinB1 are expressed in primary prostate epithelial cells.
  
  
  CONCLUSIONS
  PlexinB1 signals via ErbB2 to increase the invasive phenotype of prostate cancer cells. Both wild-type and mutant forms of plexinB1 are potential targets for anti-cancer therapy in prostate tumors that express ErbB2.
authors.affiliation: Prostate Cancer Research Centre, University College London, London, UK.
authors.forename: Adebiyi
authors.initials: A
authors.lastname: Damola
authors.forename: Anne
authors.initials: A
authors.lastname: Legendre
authors.forename: Stephen
authors.initials: S
authors.lastname: Ball
authors.forename: John R
authors.initials: JR
authors.lastname: Masters
authors.forename: Magali
authors.initials: M
authors.lastname: Williamson
mesh_terms: D000818:Animals; D019556:COS Cells; D002522:Chlorocebus aethiops; D006801:Humans; D008297:Male; D009154:Mutation; D009419:Nerve Tissue Proteins / Q000235:genetics* / Q000502:physiology*; D011471:Prostatic Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000503:physiopathology; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000502:physiology*; D014407:Tumor Cells, Cultured
chemical_list: D009419:Nerve Tissue Proteins; C492119:PLXNB1 protein, human; D011956:Receptors, Cell Surface
keywords: ErbB2; c-Met; cell motility; invasion; semaphorin