title: CRBP-1 expression in ovarian cancer: a potential therapeutic target.
abstract: OBJECTIVE
  Cellular retinol binding protein-1 regulates retinol bioavailability and contributes to cell differentiation maintenance, but its role in ovarian carcinogenesis remains uncertain. We investigated CRBP-1 expression in ovarian tumors and CRBP-1 signaling-regulated pathways.
  
  
  METHODS
  We performed immunohistochemistry, methylation-specific PCR, gene copy number analysis in ovarian tumors and proliferation/apoptosis evaluation, gene array, blot and real-time PCR in CRBP-1-transfected A2780 ovarian cancer cells.
  
  
  RESULTS
  CRBP-1 expression was reduced or absent in G2 and G3 ovarian carcinomas. CRBP-1 silencing in 60% of G2 and 66.7% of G3 carcinomas was due to CRBP-1 promoter methylation. A2780 CRBP-1-transfected cells showed increased retinol-induced apoptosis, retinoid-induced reduced clonogenicity and down-regulation of proliferation and transcription genes, including AKT1, AKT3, EGFR, FOS, JUN, STAT1 and STAT5A.
  
  
  CONCLUSIONS
  CRBP-1 loss in G2/G3 ovarian carcinomas and increased apoptotic susceptibility to retinoids in CRBP-1-transfected-A2780 cells suggest CRBP-1 screening as a target to ensure efficacy of an adjuvant retinoid therapy.
authors: Anatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy.
authors: Elena
authors: E
authors: Doldo
authors: Anatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy.
authors: Gaetana
authors: G
authors: Costanza
authors: Anatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy.
authors: Amedeo
authors: A
authors: Ferlosio
authors: Anatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy.
authors: Daniela
authors: D
authors: Passeri
authors: Department of Laboratory Medicine, Tor Vergata University of Rome, Rome, Italy.
authors: Sergio
authors: S
authors: Bernardini
authors: Anatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy.
authors: Maria Giovanna
authors: MG
authors: Scioli
authors: Anatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy.
authors: Donatella
authors: D
authors: Mazzaglia
authors: Anatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy.
authors: Sara
authors: S
authors: Agostinelli
authors: Experimental Chemotherapy Laboratory, Regina Elena National Cancer Institute, Rome, Italy.
authors: Donatella
authors: D
authors: Del Bufalo
authors: Patho-Lab Diagnostics, Ness-Zione, Israel.
authors: Bernard
authors: B
authors: Czernobilsky
authors: Anatomic Pathology, Department of Biomedicine and Prevention, Tor Vergata University of Rome, Rome, Italy orlandi@uniroma2.it.
authors: Augusto
authors: A
authors: Orlandi
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D019175:DNA Methylation; D005260:Female; D018628:Gene Dosage; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D061986:MCF-7 Cells; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D011401:Promoter Regions, Genetic; D046988:Proteasome Endopeptidase Complex / Q000378:metabolism; D054840:Retinol-Binding Proteins, Cellular / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction; D046888:Tissue Array Analysis; D014801:Vitamin A / Q000494:pharmacology
chemical_list: D054840:Retinol-Binding Proteins, Cellular; D014801:Vitamin A; D046988:Proteasome Endopeptidase Complex
keywords: Retinol; apoptosis; gynecological cancer; ovarian tumor; retinol binding protein