Department of Pathology, Hamamatsu University School of Medicine, Higashi-ward, Hamamatsu 431-3192, Japan.
Int J Oncol. 2010 Mar;36(3):635-40.
EPHA7 is a member of the EPHA family of receptor kinases, among which several members are known to be involved in human lung carcinogenesis. We report here a novel spliced variant, the so-called secreted form of EPHA7, recently reported in malignant lymphoma, in human lung cancer cell lines and primary lung cancer. In contrast to the EPHA7 down-regulation in colorectal cancer by promoter hypermethylation, EPHA7 is expressed at a substantial level in most human lung cancers and the secreted form of EPHA7 mRNA was found in a fraction of primary lung cancer tissues, lung cancer cell lines, and immortalized bronchogenic epithelial cell lines. Interestingly, the secreted form of EPHA7 message was predominantly detected in non-adeno type lung carcinoma. The mechanistic role of the secreted form of EPHA7 in human lung carcinogenesis is not clear, but the presence of this form could distinctly exclude adenocarcinoma of the lung from the other categories, i.e., squamous cell carcinoma, small cell carcinoma and large cell carcinoma, which have strong association with smoking. This is the first study to detect the secreted form of EPHA7 in human epithelial tissues. EPHA7 warrants further investigation to determine its possible involvement in smoking related lung carcinogenesis.
Epha7 是 Eph 受体激酶家族的成员之一，其中一些成员已知参与人类肺癌的发生。我们在此报告一种新的剪接变异体，即最近在恶性淋巴瘤、人肺癌细胞系和原发性肺癌中报道的所谓 Epha7 的分泌形式。与启动子超甲基化导致结直肠癌中 EphA7 下调相反，Epha7 在大多数人类肺癌中表达水平较高，并且在一部分原发性肺癌组织、肺癌细胞系和永生化支气管上皮细胞系中发现了 EphA7 mRNA 的分泌形式。有趣的是，Epha7 分泌形式主要在非腺癌中检测到。Epha7 分泌形式在人类肺癌发生中的机制作用尚不清楚，但这种形式的存在可以明显将肺癌与其他类型（即鳞状细胞癌、小细胞癌和大细胞癌）区分开来，这些类型与吸烟有很强的关联。这是首次在人上皮组织中检测到 EphA7 的分泌形式。Epha7 需要进一步研究以确定其在与吸烟相关的肺癌发生中的可能参与。
