EPHA2/EFNA1 expression in human gastric cancer
EPHA2/EFNA1 expression in human gastric cancer
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DOI：
10.1111/j.1349-7006.2005.00007.x
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发表时间：
2005-01-01
期刊：
影响因子：
5.7
通讯作者：
Sugimura, H
中科院分区：
文献类型：
--
作者：
Nakamura, R;Kataoka, H;Sugimura, H
促红细胞生成素产生肝细胞（EPH）A2受体酪氨酸激酶在几种类型的人类肿瘤中过度表达和磷酸化，并与恶性转化有关。然而，最近的一份报告表明，刺激EPHA2受体配体ephrinA1 （EFNA1）可抑制表达EPHA2的乳腺癌的生长。作者采用半定量逆转录聚合酶链反应（RT-PCR）检测了EPHA2和EFNA1在4种胃癌细胞系和49份原发胃癌样本以及正常胃组织中的表达。27例（55%）肿瘤组织中EPHA2表达高于正常组织。EFNA1在肿瘤组织中过表达28例（57%）。未发现表达水平与肿瘤大小、年龄、血管浸润或淋巴结受累等组织学特征有显著相关性。但EPHA2过表达在肉眼可见的3型和4型肿瘤中比在1型和2型进展期胃癌中更为突出。作者观察到EPHA2在四种胃癌细胞系（AGS、KATO3和MKN74）中的三种中表达。在一个细胞系中，通过northern blotting、RT-PCR和western blotting几乎检测不到TMK1、EPHA2的表达。相比之下，EFNA1在所有细胞系中均检测到。在内源性表达EPHA2的胃癌细胞系中，ephrinA1-Fc刺激导致EPHA2蛋白表达降低，EPHA2磷酸化升高。最后，用可溶性ephrinA1-Fc反复刺激epha2表达细胞，抑制其生长。综上所述，这些发现提示EPHA2和EFNA1的表达可能影响人类胃癌的行为。
The erythropoietin-producing hepatocellular (EPH)A2 receptor, tyrosine kinase, is overexpressed and phosphorylated in several types of human tumors and has been associated with malignant transformation. A recent report, however, indicated that stimulation of the EPHA2 receptor ligand, ephrinA1 (EFNA1), inhibits the growth of EPHA2-expressing breast cancer. The authors examined the expression of EPHA2 and EFNA1 using semiquantitative reverse transcription-polymerase chain reaction (RT-PCR) in four gastric cancer cell lines and 49 primary gastric cancer samples, as well as in normal gastric tissue. EPHA2 was more highly expressed in tumor tissue than in normal tissue in 27 cases (55%). EFNA1 was overexpressed in tumor tissue in 28 cases (57%). No significant correlation was detected between the expression levels and histologic features such as tumor size, age, vessel invasion, or lymph node involvement. However, EPHA2 overexpression was more prominent in macroscopic type 3 and 4 tumors than in type 1 or 2 advanced gastric cancer. The authors observed EPHA2 expression in three of the four gastric cancer cell lines (AGS, KATO3, and MKN74) that were examined. In one cell line, TMK1, EPHA2 expression was barely detectable using northern blotting, RT-PCR, and western blotting. In contrast, EFNA1 was detected in all cell lines. In the gastric cancer cell lines that endogenously expressed EPHA2, stimulation with ephrinA1-Fc led to decreased EPHA2 protein expression and increased EPHA2 phosphorylation. Finally, the growth of EPHA2-expressing cells was inhibited by repetitive stimulation with soluble ephrinA1-Fc. Taken together, these findings suggest that EPHA2 and EFNA1 expression may influence the behavior of human gastric cancer.