TY - JOUR
T1 - CRBP-1 expression in ovarian cancer
T2 - A potential therapeutic target
AU - Doldo, Elena
AU - Costanza, Gaetana
AU - Ferlosio, Amedeo
AU - Passeri, Daniela
AU - Bernardini, Sergio
AU - Scioli, Maria Giovanna
AU - Mazzaglia, Donatella
AU - Agostinelli, Sara
AU - Del Bufalo, Donatella
AU - Czernobilsky, Bernard
AU - Orlandi, Augusto
PY - 2014/7/1
Y1 - 2014/7/1
N2 - Background/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.
AB - Background/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.
KW - Apoptosis
KW - Gynecological cancer
KW - Ovarian tumor
KW - Retinol
KW - Retinol binding protein
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M3 - Article
C2 - 24982334
AN - SCOPUS:84906314069
VL - 34
SP - 3303
EP - 3312
JO - Anticancer Research
JF - Anticancer Research
SN - 0250-7005
IS - 7
ER -