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CRBP-1 expression in ovarian cancer: a potential therapeutic target.

AbstractBACKGROUND/AIM:
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.
MATERIALS AND 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.
CONCLUSION:
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.
AuthorsElena Doldo, Gaetana Costanza, Amedeo Ferlosio, Daniela Passeri, Sergio Bernardini, Maria Giovanna Scioli, Donatella Mazzaglia, Sara Agostinelli, Donatella Del Bufalo, Bernard Czernobilsky, Augusto Orlandi
JournalAnticancer research (Anticancer Res) Vol. 34 Issue 7 Pg. 3303-12 (Jul 2014) ISSN: 1791-7530 [Electronic] Greece
PMID24982334 (Publication Type: Journal Article)
CopyrightCopyright© 2014 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.
Chemical References
  • Retinol-Binding Proteins, Cellular
  • Vitamin A
  • Proteasome Endopeptidase Complex
Topics
  • Adult
  • Aged
  • Aged, 80 and over
  • Cell Growth Processes (genetics)
  • Cell Line, Tumor
  • DNA Methylation
  • Female
  • Gene Dosage
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunohistochemistry
  • MCF-7 Cells
  • Middle Aged
  • Ovarian Neoplasms (drug therapy, genetics, metabolism)
  • Promoter Regions, Genetic
  • Proteasome Endopeptidase Complex (metabolism)
  • Retinol-Binding Proteins, Cellular (biosynthesis, genetics)
  • Signal Transduction
  • Tissue Array Analysis
  • Vitamin A (pharmacology)

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