Down-regulation of Bax-interacting factor-1 in colorectal adenocarcinoma.
Down-regulation of Bax-interacting factor-1 in colorectal adenocarcinoma.
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DOI：
10.1002/cncr.23892
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发表时间：
2008-11-15
期刊：
影响因子：
6.2
通讯作者：
Wang, Hong-Gang
中科院分区：
文献类型：
--
作者：
Coppola, Domenico;Khalil, Farah;Eschrich, Steven A.;Boulware, David;Yeatman, Timothy;Wang, Hong-Gang
Bif-1蛋白是内亲素B家族的成员，在细胞凋亡、自噬和线粒体形态学中起关键作用。Bif-1的缺失抑制程序性细胞死亡并促进肿瘤发生。Bif-1与结直肠癌的关系仍有待评估。为了检测Bif-1在人结直肠腺癌（CRC）中的表达，我们使用包含102个不同分期的CRC和38个正常结直肠粘膜（NR）样本的分期定向癌组织芯片进行免疫组织化学。使用抗生物素蛋白-生物素-过氧化物酶方法和抗Bif-1鼠单克隆抗体对组织阵列上的福尔马林固定、石蜡包埋的核心切片进行免疫染色。BIF-1染色由两名独立的观察者评分。为了检测Bif-1 mRNA水平，我们对205例CRC和10例NR样本进行了DNA微阵列分析。22.5%（23/102）的大肠癌组织中Bif-1表达阴性。36.3%（37/102）的肿瘤组织中Bif-1呈中到强染色，41.2%（42/102）的肿瘤组织中Bif-1呈弱染色。38例NR中26例（68.4%）表现出中等至强的Bif-1免疫反应性，无一例为阴性。12例（31.6%）NR呈弱阳性。CRC和NR的平均（中位）评分存在显着差异[分别为3.2（3.0）和5.2（6.0），p=0.0003]，NR和CRC之间阴性表达病例的百分比也存在显着差异（p=0.002）。通过微阵列分析，在mRNA水平上证实CRCs中Bif-1表达降低。我们报告了在从NR到CRC的过渡过程中Bif-1的下调，这是一个与Bif-1的肿瘤抑制功能一致的新发现。利用基因表达谱和免疫组化技术，我们证实了Bif-1在正常结肠粘膜向腺癌转变过程中的下调。
Bif-1 protein is a member of the endophilin B family that plays a critical role in apoptosis, autophagy and mitochondrial morphology. Loss of Bif-1 suppresses programmed cell death and promotes tumorigenesis. The connection of Bif-1 to colorectal cancer remains to be evaluated. To determine Bif-1 expression in human colorectal adenocarcinoma (CRC), we performed immunohistochemistry using stage oriented cancer tissue microarrays containing 102 CRC of different stage, and 38 samples of normal colorectal mucosa (NR). Formalin-fixed, paraffin-embedded core sections on the tissue array were immunostained using the avidin-biotin-peroxidase method and the anti-Bif-1 murine monoclonal antibody. Bif-1 staining was scored by two independent observers. To examine Bif-1 mRNA levels, we performed DNA microarray analysis of 205 CRC and 10 NR samples. Bif-1 expression was negative in 22.5% (23/102) of CRC. Moderate to strong Bif-1 staining was identified in 36.3% (37/102) of the tumors, and weak stain was seen in 41.2% (42/102) of them. Twenty-six of 38 (68.4%) NR samples exhibited moderate to strong Bif-1 immunoreactivity, and none of them was negative. In 12 cases (31.6%) NR showed weak Bif-1 stain. The mean (median) scores for CRCs and NR differed significantly [3.2 (3.0) and 5.2 (6.0) respectively, p=0.0003], and the percent of cases with negative expression also differed significantly between NR and CRC (p=0.002). Decreased Bif-1 expression in CRCs was confirmed at mRNA level by microarray analysis. We report the down regulation of Bif-1 during the transition from NR to CRC, a novel finding in agreement with the tumor suppressor function of Bif-1. Using gene expression profiling and immunohistochemistry we demonstrated the down regulation of Bif-1during the transition from normal colonic mucosa to adenocarcinoma.
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影响因子：
56.9
作者：
NISHISHO, I;NAKAMURA, Y;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
影响因子：
4.8
作者：
Cuddeback, SM;Yamaguchi, H;Wang, HG
通讯作者：
Wang, HG
影响因子：
7.8
作者：
Karbowski, Mariusz;Jeong, Seon-Yong;Youle, Richard J
通讯作者：
Youle, Richard J
影响因子：
--
作者：
Roberts, T;Chernova, O;Cowell, JK
通讯作者：
Cowell, JK
影响因子：
--
作者：
Bello, MJ;de Campos, JM;Rey, JA
通讯作者：
Rey, JA