Heterogeneous expression of DNA-dependent protein kinase in esophageal cancer and normal epithelium.
Heterogeneous expression of DNA-dependent protein kinase in esophageal cancer and normal epithelium.
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DOI：
10.3892/ijmm.18.3.441
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发表时间：
2006-09
影响因子：
5.4
通讯作者：
Norio Tonotsuka;Y. Hosoi;S. Miyazaki;G. Miyata;Kou Sugawara;Takahiro Mori;N. Ouchi;S. Satomi
中科院分区：
文献类型：
--
作者：
Norio Tonotsuka;Y. Hosoi;S. Miyazaki;G. Miyata;Kou Sugawara;Takahiro Mori;N. Ouchi;S. Satomi
采用Western blotting和免疫组化方法检测13例原发性食管癌患者食管癌组织和癌旁正常粘膜DNA依赖性蛋白激酶（DNA-PK）活性的定量差异以及Ku70、Ku80和DNA-PKcs蛋白表达的定量差异。肿瘤组织表现出比正常粘膜更高的DNA-PK活性。 Ku70、Ku80 和 DNA-PKcs 的蛋白水平与肿瘤组织中的 DNA-PK 活性相关。免疫组织化学分析显示，Ku70、Ku80 和 DNA-PKcs 主要位于肿瘤组织和正常粘膜的细胞核中。在正常上皮细胞中，Ku70、Ku80和DNA-PKcs仅在基底细胞层的细胞核中表达，而在腔细胞层的细胞核中不表达。在肿瘤组织中，DNA-PK蛋白的表达呈现瘤内异质性。同一肿瘤的不同部位DNA-PK蛋白的表达水平不同，甚至每个肿瘤细胞的表达水平也不同。这些结果表明细胞分化和肿瘤进展影响细胞 DNA-PK 蛋白水平及其活性。此外，食管癌细胞/组织中DNA-PK蛋白表达的瘤内异质性也表明通过估计肿瘤样本中DNA-PK活性/蛋白水平来预测肿瘤的放射或化学敏感性是困难的。
Esophageal cancer tissues and adjacent normal mucosae in 13 patients with primary esophageal cancer were examined for quantitative differences in DNA-dependent protein kinase (DNA-PK) activity and for expressions of Ku70, Ku80 and DNA-PKcs proteins by Western blotting and immunohistochemistry. The tumor tissues showed higher DNA-PK activity than the normal mucosae. Protein levels of Ku70, Ku80 and DNA-PKcs correlated with DNA-PK activities in the tumor tissues. Immunohistochemical analysis revealed that Ku70, Ku80 and DNA-PKcs located predominantly in the nuclei in both the tumor tissues and normal mucosae. In the normal epithelium, Ku70, Ku80 and DNA-PKcs were expressed only in the nuclei of the basal cell layers and not in those of the lumenal cell layers. In the tumor tissues, the expressions of DNA-PK proteins showed intratumoral heterogeneity. The different portions in the same tumor showed different expression levels of DNA-PK proteins, and even each tumor cell showed different expression levels. These results suggest that cell differentiation and tumor progression affect cellular DNA-PK protein levels and its activity. Furthermore, the intratumoral heterogeneity of DNA-PK protein expression in esophageal cancer cells/ tissues also suggests the difficulty in prediction of radio- or chemo-sensitivity of the tumor through estimation of DNA-PK activity/protein levels in tumor specimens.