title: Fimbrial cells exposure to catalytic iron mimics carcinogenic changes.
abstract: OBJECTIVE
  Recent evidence strongly suggests that the fallopian tube is a site of origin of ovarian cancer. Although histological data show iron deposition in the fallopian tubes, its role remains unclear. To establish whether catalytic iron has a possible role in ovarian carcinogenesis, we isolated human fimbrial secretory epithelial cells (FSECs).
  
  
  METHODS
  Fimbrial secretory epithelial cells, isolated from women undergoing isteroannessiectomy, were treated with different doses of catalytic iron (0.05-100 mM) to study cell viability; NO production; p53, Ras, ERK/MAPK, PI3K/Akt, Ki67, and c-Myc protein expressions through Western blot analysis; and immunocytochemistry or immunofluorescence.
  
  
  RESULTS
  In FSECs treated with catalytic iron for up to 6 days, we observed an increase in cell viability, NO production, and p53, pan-Ras, ERK/MAPK, PI3K/Akt, Ki67, and c-Myc activations (P < 0.05) in a dose-dependent and time-dependent manner. These same results were also observed in FSECs maintained for respectively 2 and 4 weeks in the absence of catalytic iron after 6 days of stimulation.
  
  
  CONCLUSIONS
  Our model aimed at studying the main nongenetic risk factor for ovarian cancer, providing an alternative interpretation for the role of menstruation in increasing risk of this pathology. This in vitro model mimics several features of the precursor lesions and opens new scenarios for further investigations regarding the correlation between damages produced by repeated retrograde menstruation carcinogenic stimuli.
authors.affiliation: *Department of Obstetrics and Gynecology, Fondazione IRCCS Ca Granda, Ospedale Maggiore Policlinico, Milan; †Unit of Pathology, Department of Health Sciences, and ‡Physiology Laboratory, Department of Translational Medicine, University of Eastern Piedmont "Amedeo Avogadro," Novara, Italy.
authors.forename: Debora
authors.initials: D
authors.lastname: Lattuada
authors.forename: Francesca
authors.initials: F
authors.lastname: Uberti
authors.forename: Barbara
authors.initials: B
authors.lastname: Colciaghi
authors.forename: Vera
authors.initials: V
authors.lastname: Morsanuto
authors.forename: Elena
authors.initials: E
authors.lastname: Maldi
authors.forename: Diletta Francesca
authors.initials: DF
authors.lastname: Squarzanti
authors.forename: Claudio
authors.initials: C
authors.lastname: Molinari
authors.forename: Renzo
authors.initials: R
authors.lastname: Boldorini
authors.forename: Alessandro
authors.initials: A
authors.lastname: Bulfoni
authors.forename: Paola
authors.initials: P
authors.lastname: Colombo
authors.forename: Giorgio
authors.initials: G
authors.lastname: Bolis
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000139:chemically induced; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004847:Epithelial Cells / Q000737:chemistry / Q000187:drug effects* / Q000473:pathology; D048049:Extracellular Signal-Regulated MAP Kinases / Q000032:analysis; D005187:Fallopian Tubes / Q000166:cytology; D005260:Female; D006801:Humans; D007501:Iron / Q000008:administration & dosage / Q000009:adverse effects*; D019394:Ki-67 Antigen / Q000032:analysis; D008954:Models, Biological; D009569:Nitric Oxide / Q000096:biosynthesis; D018384:Oxidative Stress / Q000187:drug effects; D019869:Phosphatidylinositol 3-Kinases / Q000032:analysis; D051057:Proto-Oncogene Proteins c-akt / Q000032:analysis; D016271:Proto-Oncogene Proteins c-myc / Q000032:analysis; D016159:Tumor Suppressor Protein p53 / Q000032:analysis; D018631:ras Proteins / Q000032:analysis
chemical_list: D019394:Ki-67 Antigen; C489427:MYC protein, human; D016271:Proto-Oncogene Proteins c-myc; D016159:Tumor Suppressor Protein p53; D009569:Nitric Oxide; D007501:Iron; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D048049:Extracellular Signal-Regulated MAP Kinases; D018631:ras Proteins