Abstract. carbonyl reductase 1 (cBr1) expression level is related to tumor progression. Decreased cBr1 expression is associated with poor prognosis in ovarian cancer. We investigated the relationship between cBr1 expression level and malignant potential of ovarian cancer. oVcar-3 cells overexpressing cBr1 or knocked down for cBr1 were obtained by transfecting cBr1 plasmid Dna (pDna) or small interfering rna (sirna) by electroporation. In vitro cell proliferation and invasion were compared between the two cell types. Subcutaneous cBr1-overexpressed oVcar-3 cells (n=10) and wild-type ones (n=5) were injected into nude mice. the cBr1 sirna was then injected twice a week into five of the 10 CBR1-overexpressed OVCAR-3 tumors. Tumor growth and metastatic behavior were observed 3 weeks after cell transplantation. cell proliferation significantly decreased in cBr1-overexpressed cells as compared to the control, whereas cell proliferation and invasion significantly increased in cBr1-suppressed cells as compared to the control. the size of the cBr1 sirna-injected tumors (n=5) increased significantly as compared to the other two groups (n=5 for each group). the number of metastatic foci in the lungs was significantly higher in mice injected with cBr1 sirna (7.0±2.0) compared to cBr1-overexpressed and wild-type tumors (0 and 2.0±2.0, respectively). Western blot analysis showed that, while vascular endothelial growth factor (Vegf)-c expression was stable in the cBr1-sirna-injected tumors, e-cadherin expression was decreased, whereas matrix metalloproteinase (MMP)-9 was increased in cBr1-sirna-injected tumors compared to the other two groups. these results showed that cBr1 decreases promoted tumor proliferation and growth as well as invasion and metastasis, suggesting that cBr1 has potential to become a new candidate for molecular targeting therapy.

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Background: The human RECQ DNA helicase family is involved in genomic stability. Gene mutations of RECQL2, RECQL3, and RECQL4 are associated with genetic disorders and induce early aging and carcinogenesis. Although previous studies have reported that the level of RECQL1 expression is correlated with the prognosis of some of malignancies, the function of RECQL1 is not yet clarified. The present study aimed to examine the relationship between prognosis and the level of RECQL1 expression in epithelial ovarian cancer (EOC), and to identify the role of RECQL1 in EOC cells. Methods: The level of RECQL1 expression was determined immunohistochemically in 111 patients with EOC who received initial treatment at Hirosaki University hospital between 2006 and 2011. Effects of RECQL1 on cell growth or apoptosis were examined in vitro using wild-type and OVCAR-3 cells (RECQL1(+) cells) and similar cells transfected with RECQL1 siRNA transfected (RECQL1(−) cells).

BackgroundThe human RECQ DNA helicase family is involved in genomic stability. Gene mutations of RECQL2, RECQL3, and RECQL4 are associated with genetic disorders and induce early aging and carcinogenesis. Although previous studies have reported that the level of RECQL1 expression is correlated with the prognosis of some of malignancies, the function of RECQL1 is not yet clarified. The present study aimed to examine the relationship between prognosis and the level of RECQL1 expression in epithelial ovarian cancer (EOC), and to identify the role of RECQL1 in EOC cells.MethodsThe level of RECQL1 expression was determined immunohistochemically in 111 patients with EOC who received initial treatment at Hirosaki University hospital between 2006 and 2011. Effects of RECQL1 on cell growth or apoptosis were examined in vitro using wild-type and OVCAR-3 cells (RECQL1(+) cells) and similar cells transfected with RECQL1 siRNA transfected (RECQL1(−) cells).ResultsThe level of RECQL1 expression was not related to histological type, clinical stage, or retroperitoneal lymph node metastasis, but the expression level was significantly higher (P = 0.002) in patients with recurrence than those without recurrence, and progression-free survival and complete response rate to chemotherapy were also improved in patients with RECQL1-low expression (n = 39) stage III/IV EOC (P = 0.02 and P <0.05 vs RECQL1-high expression patients (n = ), respectively). A cell proliferation and colony formation assays revealed significantly less growth of RECQL1(−) cells compared to RECQL1(+) cells. A flow cytometry using annexin V -FITC and propidium iodide (PI) staining revealed a significant increase in apoptotic RECQL1(−) cells. Cell cycle analysis showed a significantly greater distribution in subG1 phase indicating apoptotic cells in RECQL1(−) cells than in RECQL1(+) cells.ConclusionsThese results suggest that RECQL1 is a prognostic factor for EOC and that RECQL1 contributes to potential malignancy by inhibiting apoptosis.