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ITM2A, down-regulated in serous ovarian cancer patients has anti-tumoral activity of ovarian cancer cells by inducing G2/M cell cycle arrest
( Thi My Hien Nguyen ) , ( Tae Jin Lee ) , ( Jun Soo Park ) , ( Sang Hoon Lee ) , ( Dong Ho Kim ) , ( Hyung Moo Park ) , ( Gwang Jun Kim ) , ( Eun Ju Lee )
UCI I410-ECN-0102-2015-500-000096259
이 자료는 4페이지 이하의 자료입니다.

목적: The aim of this study is to assess ITM2A expression in normal and cancer originated from ovary and to determine its role in ovarian cancer. 방법: ITM2A expression was evaluated by cDNA microarray, real-time PCR, and Western analysis of frozen tissues and by immunohistochemical analysis of paraffin blocks. For immunihistochemical analysis, ninety patients with primary invasive ovarian serous adenocarcinoma were included in this study. Thirty-five normal ovaries, 20 serous adenomas and 11 serous tumors with low malignancy potential (LMP) were used as controls. Clinical and pathologic findings were obtained from the medical records. To determine the effects of ITM2A on ovarian cancer cells, CKK-8 assay, colony formation assay, cell cycle analysis, and in vivo study were carried out using transiently treanfected cells or stable clones. Survival data were estimated using Kaplan-Meier estimates and compared with the log-rank test. Multivariate analysis was performed using the Cox-regression method. Student`s t test was used to compare values betwee two groups. 결과: cDNA microarray, real-time PCR, Western analysis and immunohistochemical analysis showed down-regulation of ITM2A in ovarian cancer compared with normal, benign and LMP samples. ITM2A expression was absent in 41 (45.6%) of 90 ovarian cancer patients. ITM2A absence was more frequent in the patients with advanced stage, suboptimal debulking operation, disease recurrence and platinum resistance (p=0.012, p=0.019, p=0.013 and p<0.02, respectively). Multivariate analysis showed that advanced and loss of ITM2A were independent factors related to poor prognosis (p=0.025 and p=0.016, respectively). CKK-8 assay, colony formation assay, and in vivo study showed that over-expression of ITM2A in TOV-21G ovarian cancer cells inhibited cell proliferationIn. Cell cycle analysis showed that ITM2A induced G2/M phase arrest. Accordingly, decreased expression of cyclin B1, phospho-cdc2, and cdc25c were observed in ITM2A over-expressing cells. 결론: ITM2A is frequently down-regulated in invasive epithelial ovarian cancer and is independent poor prognostic factors of invasive ovarian serous carcinoma. ITM2A has anti-tumoral activity of ovarian cancer cells by G2/M cell cycle arrest.

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