Nup88 mRNA overexpression is associated with high aggressiveness of breast cancer
Nup88 mRNA overexpression is associated with high aggressiveness of breast cancer
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DOI：
10.1002/ijc.20034
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发表时间：
2004-05-01
影响因子：
6.4
通讯作者：
Schneider, J
中科院分区：
文献类型：
--
作者：
Agudo, D;Gómez-Esquer, F;Schneider, J
核孔复合蛋白 Nup88 在肿瘤细胞中过度表达。免疫组织化学研究表明，这种过度表达与结直肠癌的更高侵袭性和黑色素瘤细胞转移潜力的增强有关。然而，迄今为止针对Nup88开发的抗体具有识别除Nup88之外的许多其他、迄今为止未指定的抗原的缺点。为此，我们设计了本研究，在 mRNA 水平上研究 Nup88 的表达。从 122 名乳腺癌患者对应的新鲜肿瘤组织中提取 RNA。通过差异 RT-PCR 测量 Nup88 mRNA 表达，并针对组成型内部对照基因（β-肌动蛋白）进行标准化。使用中值作为截止值，将结果分为“高”和“低”表达水平。高 Nup88 mRNA 表达水平与导管和肾小管组织学 (p = 0.012)、肿瘤组织学和核 3 级 (p < 0.001)、缺乏激素受体表达 (p < 0.001)、c-erb-B2 癌基因表达 (p < 0.001)、突变 p53 蛋白表达 (p < 0.001)、高增殖（由 Ki67 定义）显着相关标记指数> 20％，p < 0.001），DNA非整倍体（p < 0.001）以及最重要的不祥的临床预后因素，腋窝淋巴结侵犯（p < 0.001）。我们还发现与 H-NIAM（乳房珠蛋白）基因的表达呈负相关（p < 0.001），该基因是乳腺癌低生物学和临床侵袭性的标志。所有这些因素无一例外地定义了高度侵袭性的肿瘤表型。这些发现似乎是 Nup88 特有的，而不是一般的核孔蛋白。事实上，在相同条件下、相同肿瘤中对 Nup107（核孔复合物的限制成分）的分析并未产生可比较的结果。 (C) 2004 年威利利斯。公司
The nuclear pore complex protein Nup88 is overexpressed in tumor cells. Immunohistochemical studies have shown that this overexpression is linked to higher aggressiveness of colorectal carcinoma and to enhanced metastatic potential of melanoma cells. However, the antibodies so far developed against Nup88 have the drawback of recognizing a number of other, up to now unspecified antigens besides Nup88. For this reason, we devised the present study on Nup88 expression at the mRNA level. RNA was extracted from fresh tumor tissue corresponding to 122 breast cancer patients. Nup88 mRNA expression was measured by means of differential RT-PCR, standardizing against a constitutive internal control gene (beta-actin). The results were dichotomized into "high" and "low" expression levels, using the median value as cut-off. High Nup88 mRNA expression levels correlated significantly with ductal and tubular histology (p = 0.012), histologic and nuclear grade 3 of tumors (p < 0.001), absence of hormone receptor expression (p < 0.001), expression of the c-erb-B2 oncogene (p < 0.001), expression of mutant p53 protein (p < 0.001), high proliferation (defined by Ki67 labeling index >20%, p < 0.001), DNA aneuploicly (p < 0.001) as well as the most important ominous clinical prognostic factor, axillary node invasion (p < 0.001). We also found an inverse correlation (p < 0.001) with expression of the H-NIAM (mammaglobin) gene, a marker of low biologic and clinical aggressiveness of breast cancer. All of these factors, without exception, define a highly aggressive tumor phenotype. These findings appear to be specific to Nup88 and not to nuclear pore proteins in general. Indeed, analysis of Nup107 (which is a limiting component of the nuclear pore complex) under the same conditions in the same tumors did not yield comparable results. (C) 2004 Wiley-Liss. Inc.