title: Opioid antagonist-induced regulation of the mu-opioid receptor expression in MCF-7 breast cancer cell line.
abstract: OBJECTIVE
  In our earlier study we have demonstrated that MCF-7 cell line expresses all three opioid receptor types, micro, delta and kappa (MOR, DOR and KOR, respectively), but predominantly MOR. Morphine, as well as endogenous MOR-selective agonists, endomorphin-1 and endomorphin-2 were shown to decrease MOR gene expression in MCF-7 cells. Opioid antagonist - naloxone -produced the opposite effect, increasing MOR gene expression. In this study we investigated and compared the influence of several opioid antagonists of alkaloid structure (beta-funaltrexamine and naloxonazine) and of peptide structure: [Dmt(1), D-1-Nal(4)]endomorphin-2, [Dmt, D-2-Nal(4)]endomorphin-1, and [Dmt, D-2-Nal(4)]endomorphin-2 on MOR up-/down-regulation and proliferation in MCF-7 cell line.
  
  
  METHODS
  MCF-7 cells were incubated with opioids. The levels of MOR mRNA were assessed using quantitative real-time RT-PCR assay. Cell growth was measured by Mosmann tetrazolium salt assay.
  
  
  RESULTS
  It was shown that all tested opioid antagonists produced up-regulation of MOR gene expression, but the strongest effect was observed with naloxonazine. However, none of the antagonists at concentrations as high as 10(-4) M showed any antiproliferative effects on MCF-7 cells, neither in the presence or absence of beta-estradiol.
  
  
  CONCLUSIONS
  It seems that up- or down-regulation of MOR mRNA levels has no direct effect on cell proliferation.
authors.affiliation: Laboratory of Biomolecular Chemistry, Medical University of Lodz, Lodz, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Gach
authors.forename: Mariola
authors.initials: M
authors.lastname: Piestrzeniewicz
authors.forename: Jakub
authors.initials: J
authors.lastname: Fichna
authors.forename: Janusz
authors.initials: J
authors.lastname: Szemraj
authors.forename: Anna
authors.initials: A
authors.lastname: Janecka
mesh_terms: D001943:Breast Neoplasms / Q000737:chemistry / Q000378:metabolism* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004958:Estradiol / Q000494:pharmacology; D006801:Humans; D009270:Naloxone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D017450:Receptors, Opioid, mu / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D009292:Narcotic Antagonists; D012333:RNA, Messenger; D017450:Receptors, Opioid, mu; D009270:Naloxone; D004958:Estradiol; C034643:naloxonazine