CRBP-1 expression in ovarian cancer: A potential therapeutic target

Elena Doldo, Gaetana Costanza, Amedeo Ferlosio, Daniela Passeri, Sergio Bernardini, Maria Giovanna Scioli, Donatella Mazzaglia, Sara Agostinelli, Donatella Del Bufalo, Bernard Czernobilsky, Augusto Orlandi

Research output: Contribution to journalArticle

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 languageEnglish
Pages (from-to)3303-3312
Number of pages10
JournalAnticancer Research
Volume34
Issue number7
Publication statusPublished - Jul 1 2014

Keywords

  • Apoptosis
  • Gynecological cancer
  • Ovarian tumor
  • Retinol
  • Retinol binding protein

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

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  • Cite this

    Doldo, E., Costanza, G., Ferlosio, A., Passeri, D., Bernardini, S., Scioli, M. G., Mazzaglia, D., Agostinelli, S., Del Bufalo, D., Czernobilsky, B., & Orlandi, A. (2014). CRBP-1 expression in ovarian cancer: A potential therapeutic target. Anticancer Research, 34(7), 3303-3312.