Involvement of EphA2 in head and neck squamous cell carcinoma: mRNA expression, loss of heterozygosity and immunohistochemical studies.
Involvement of EphA2 in head and neck squamous cell carcinoma: mRNA expression, loss of heterozygosity and immunohistochemical studies.
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DOI：
10.3892/or.19.5.1079
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发表时间：
2008-05
期刊：
影响因子：
4.2
通讯作者：
R. Rivera;M. Gunduz;H. Nagatsuka;E. Gunduz;B. Cengiz;K. Fukushima;L. Beder;D. Pehlivan;N. Yamanaka-N
中科院分区：
文献类型：
--
作者：
R. Rivera;M. Gunduz;H. Nagatsuka;E. Gunduz;B. Cengiz;K. Fukushima;L. Beder;D. Pehlivan;N. Yamanaka-N
EphA2 是一种 130 kDa 的跨膜蛋白，主要存在于成人上皮细胞中，是最大的受体酪氨酸激酶之一的成员。它位于 1p36.1，癌症的遗传热点。在侵袭性实体瘤中观察到 EphA2 过度表达，并报道了其在肿瘤发生（包括细胞生长、存活、迁移和血管生成）中的潜在作用。然而，EphA2 在头颈癌中的作用仍不清楚。在这项研究中，我们通过测定 mRNA 水平、杂合性丢失状态和蛋白质表达来研究原发性头颈鳞状细胞癌 (HNSCC) 中 EphA2 的遗传特征。 mRNA 表达也与临床病理数据相关。尽管注意到肿瘤中的 mRNA 表达与正常组织相比增加了 10 倍，但观察到杂合性偶尔丢失 (20%)。在区域转移、肿瘤大小为 T3-T4 且分化程度为中度至低度的患者中观察到大量具有正常至高 mRNA 表达的样本。然而，统计研究并未显示 mRNA 表达与任何临床病理参数之间存在任何相关性。肿瘤细胞表达EphA2蛋白，但表达较弱。这些结果表明 EphA2 可能参与 HNSCC 的早期发展，但并不直接负责其进展。
EphA2 is a 130-kDa transmembrane protein primarily found in adult human epithelial cells and is a member of one of the largest receptor tyrosine kinases. It is located on 1p36.1, a genetic hot spot in cancer. EphA2 overexpression has been observed in aggressive solid tumors and its potential role in tumorigenesis, which includes cell growth, survival, migration and angiogenesis have been reported. However, the role of EphA2 remains unknown in head and neck cancer. In this study, we investigated the genetic profile of EphA2 in primary head and neck squamous cell carcinoma (HNSCC) by determining mRNA level, status of loss of heterozygosity and protein expression. mRNA expression was also correlated with clinicopathological data. Infrequent loss of heterozygosity (20%) was observed, though a 10-fold increase of mRNA expression in tumors compared to normal tissues was noted. A significant number of samples with normal to high mRNA expression was observed among patients with regional metastasis, with T3-T4 tumor size and with moderate to poor differentiation. However, statistical studies did not show any correlation between mRNA expression and any of the clinicopathological parameters. Tumor cells expressed EphA2 protein, but only weakly. These results suggest that EphA2 might be involved in the early development of HNSCC although not directly responsible for its progression.