1. CRBP-1 expression in ovarian cancer: a potential therapeutic target
- Author
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Elena, Doldo, Gaetana, Costanza, Amedeo, Ferlosio, Daniela, Passeri, Sergio, Bernardini, Maria Giovanna, Scioli, Donatella, Mazzaglia, Sara, Agostinelli, Donatella, Del Bufalo, Bernard, Czernobilsky, and Augusto, Orlandi
- Subjects
Adult ,Aged, 80 and over ,Ovarian Neoplasms ,Proteasome Endopeptidase Complex ,Gene Dosage ,Retinol-Binding Proteins, Cellular ,Cell Growth Processes ,DNA Methylation ,Middle Aged ,Immunohistochemistry ,Gene Expression Regulation, Neoplastic ,Tissue Array Analysis ,Cell Line, Tumor ,MCF-7 Cells ,Humans ,Female ,Promoter Regions, Genetic ,Vitamin A ,Aged ,Signal Transduction - Abstract
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.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.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.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.
- Published
- 2014