title: Effects of bicalutamide and 4OH-tamoxifen on androgen-regulated gene expression in the LNCaP cell line.
abstract: BACKGROUND
  Bicalutamide (BIC) is an alternative treatment to castration for advanced prostate cancer. Breast events are common adverse effects which can be effectively prevented by the concurrent administration of tamoxifen, a selective estrogen receptor modulator.
  
  
  METHODS
  We investigated the effects of BIC, 4-hydroxy Tamoxifen (4OHT), the active metabolite of tamoxifen, and their combination on the expression of a panel of genes implicated in prostate cancer development and progression in LNCaP cells stimulated with dihydrotestosterone.
  
  
  RESULTS
  Our findings confirm the anti-proliferative activity of BIC on LNCaP cell growth but also show the down-regulating function of this anti-androgen on the expression of genes involved in tumor proliferation and invasion [cyclins, caspases, epidermal growth factor (EGF)]. The combination with 4OHT exerts a synergistic effect on the downregulation of some genes involved in prostate cancer progression.
  
  
  CONCLUSIONS
  The observation that the expression of several genes [such as B-cell lymphoma-2 (BCL2), myelocytomatosis oncogene (MYC), caspases] is modulated midly-to-moderately, after 4OHT addition suggests that this combined approach in the clinical setting should be further investigated through appropriate trials.
authors.affiliation: Department of Medical Oncology, IRCCS SAN Martino Hospital - IST National Cancer Research Institute, Largo R. Benzi 10, 16132 Genoa, Italy. rosa.mangerini@istge.it
authors.forename: Rosa
authors.initials: R
authors.lastname: Mangerini
authors.forename: Francesca
authors.initials: F
authors.lastname: Argellati
authors.forename: Ulrich
authors.initials: U
authors.lastname: Pfeffer
authors.forename: Francesco
authors.initials: F
authors.lastname: Boccardo
mesh_terms: D000728:Androgens / Q000502:physiology*; D000813:Anilides / Q000008:administration & dosage / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D048708:Cell Growth Processes / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D007610:Kallikreins / Q000096:biosynthesis; D008297:Male; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy / Q000235:genetics; D009570:Nitriles / Q000008:administration & dosage / Q000494:pharmacology*; D017430:Prostate-Specific Antigen / Q000096:biosynthesis; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D013629:Tamoxifen / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D014105:Tosyl Compounds / Q000008:administration & dosage / Q000494:pharmacology*
chemical_list: D000728:Androgens; D000813:Anilides; D009570:Nitriles; D014105:Tosyl Compounds; D013629:Tamoxifen; C016601:afimoxifene; C053541:bicalutamide; C549870:KLK3 protein, human; D007610:Kallikreins; D017430:Prostate-Specific Antigen