874

CBR3

carbonyl reductase 3;CBR3;carbonyl reductase 3

NADPH-dependent carbonyl reductase 3|carbonyl reductase (NADPH) 3|carbonyl reductase [NADPH] 3|epididymis secretory protein Li 25|short chain dehydrogenase/reductase family 21C member 2|short chain dehydrogenase/reductase family 21C, member 2

21q22.2

protein-coding

We have recently reported a novel function for carbonyl reductase (CR), namely, its ability to modulate the metastatic potential of malignant mouse cells. Because there are currently no data addressing a similar function for CR in human cancers, the aim of this study was to assess a correlation between survival and metastasis, and CR level in epithelial ovarian cancer. Using anti-CR antibody, immunohistochemical staining was performed on 73 epithelial ovarian cancers, 13 borderline malignant tumours, and 25 benign ovarian tumours for a total of 111 specimens. The combined rate for strongly and weakly positive reactions for CR was 32.0% for benign tumours, 38.5% for borderline malignant tumours, and 61.6% for ovarian cancers. The CR-positive rate was 35.7% (weakly positive alone) for ovarian cancers with retroperitoneal lymph node (RLN) metastasis and 67.8% for those without RLN metastasis (P< 0.05). The 5-year survival rate was 62.7% for the patients with CR-negative cancer and 86.1% for those with CR-positive cancer (P< 0.05). The present results indicate that decreased CR expression in epithelial ovarian cancer is associated with RLN metastasis and poor survival.

To explore reasons for differences in the malignancy of tumors, we have compared two cell lines derived from a mouse lung adenocarcinoma cell line that differ 10-fold in their capacity to form lung metastases from s.c. primary tumors or after i.v. injection. One mRNA encoding carbonyl reductase was identified at a relatively high abundance in the subline with low metastatic capacity but was not detectable in the highly metastatic subline. Transfection of the former subline with a plasmid construct expressing antisense carbonyl reductase rendered the cells highly metastatic. Conversely, the capacity of the highly metastatic cells to metastasize was markedly reduced after transfection with a construct expressing carbonyl reductase. We also found that human prostate cancers show loss of carbonyl reductase expression compared with normal prostate epithelia. These data suggest that carbonyl reductase has an important function in modifying the metastatic behavior of malignant tumors.