Abstract
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.
| Original language | English |
|---|---|
| Pages (from-to) | 3303-3312 |
| Number of pages | 10 |
| Journal | Anticancer Research |
| Volume | 34 |
| Issue number | 7 |
| Publication status | Published - Jul 1 2014 |
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Keywords
- Apoptosis
- Gynecological cancer
- Ovarian tumor
- Retinol
- Retinol binding protein
ASJC Scopus subject areas
- Cancer Research
- Oncology
Cite this
CRBP-1 expression in ovarian cancer : A potential therapeutic target. / Doldo, Elena; Costanza, Gaetana; Ferlosio, Amedeo; Passeri, Daniela; Bernardini, Sergio; Scioli, Maria Giovanna; Mazzaglia, Donatella; Agostinelli, Sara; Del Bufalo, Donatella; Czernobilsky, Bernard; Orlandi, Augusto.
In: Anticancer Research, Vol. 34, No. 7, 01.07.2014, p. 3303-3312.Research output: Contribution to journal › Article
}
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
UR - http://www.scopus.com/inward/record.url?scp=84906314069&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84906314069&partnerID=8YFLogxK
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 -