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Midline2 is overexpressed and a prognostic indicator in human breast cancer and promotes breast cancer cell proliferation in vitro and in vivo
  • 分类:Q279[生物学—细胞生物学] S884.21[农业科学—特种经济动物饲养;农业科学—畜牧兽医]
  • 作者机构:[1]Department of Microbiology and Immunology, School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou 510006, China, [2]Department of Microbiology, Zhongshan School of Medicine, Sun Yat-sen University, Guangzhou 510080, China, [3]Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 510080, China
  • 相关基金:This work was supported by the National Natural Science Foundation of China (No. 81201677) and National Science and Technique Major Project (No. 201305017).
中文摘要:

Midline2 (MID2 ) 是连接到肿瘤前进和乳癌 1 的一个新奇交往搭挡的结合 ubiquitin E2 酶,早发作(BRCA1 ) 。然而,在乳癌的 MID2 的角色仍然保持未知。这研究在乳癌调查了 MID2 的表示,预示的价值,和角色。MID2 mRNA 和蛋白质的表示是显著地,在乳癌织物和确定的房间的 upregulated 在正常的胸与那相比排队上皮的房间和配对的邻近的非肿瘤织物(P < 0.001 ) 。Immunohistochemical 分析证明 MID2 是在 284 中的 272 个的 overexpressed (95.8%) paraffinembedded,转存的乳癌织物。而且,与先进临床的舞台增加的 MID2 表示(P < 0.001 ) 。高 MID2 表示显著地与先进临床的阶段和 T 被联系, N,和 M 阶段(所有 P < 0.05 ) 。Univariate 和 multivariate 分析显示那高 MID2 表情是为在全部队的差的全面幸存的一个独立预示的因素(93.73 对 172.1 个月;P < 0.001, logrank 测试) 并且在有阶段 Tis + 的亚群我 + II 和 III + IV。而且, 3-(4,5-dimethyl-2-thiazolyl )-2,5-diphenyl-2H-tetrazolium 溴化物殖民地形成,和抛锚无关的生长能力试金被进行。结果证明 MID2 表示的 siRNA silencing 显著地在 vitro 减少了 MCF-7 和 MDA-MB-231 细胞增长并且在 vivo 堵住了 MDA-MB-231 细胞异种皮移植肿瘤的生长(P < 0.05 ) 。这研究显示 MID2 可以在乳癌是一个新奇预示的标记和 interventional 目标。

英文摘要:

Midline2 (MID2) is an ubiquitin-conjugating E2 enzyme linked to tumor progression and a novel interacting partner of breast cancer 1, early-onset 0BRCA1). However, the role of MID2 in breast cancer remains unknown. This study investigated the expression, prognostic value, and role of MID2 in breast cancer. The expression of MID2 mRNA and protein was significantly upregulated in breast cancer tissue and established cell lines compared with that in normal breast epithelial cells and paired adjacent non-tumor tissue (P 〈 0.001). Immunohistochemical analysis demonstrated that MID2 was overexpressed in 272 of 284 (95.8%) paraffin- embedded, archived breast cancer tissue. Moreover, MID2 expression increased with advanced clinical stage (P 〈 0.001). High MID2 expression was significantly associated with advanced clinical stages and T, N, and M staging (all P 〈 0.05). Univariate and multivariate analyses indicated that high MID2 expression was an independent prognostic factor for poor overall survival in the entire cohort (93.73 vs. 172.1 months; P 〈 0.001, log- rank test) and in subgroups with stages Tis + Ⅰ + Ⅱ and Ⅲ + Ⅳ. Furthermore, 3-(4,5-dimethyl-2-thiazolyl)-2,5- diphenyl-2H-tetrazolium bromide colony formation, and anchorage-independent growth ability assays were conducted. Results showed that siRNA silencing of MID2 expression significantly reduced MCF-7 and MDA-MB- 231 cell proliferation in vitro and blocked the growth of MDA-MB-231 cell xenograft tumors in vivo (P 〈 0.05). This study indicated that MID2 may be a novel prognostic marker and interventional target in breast cancer.

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