Jeong Eun Goo, Lee Sung Hak, Lee Hae Woo, Soung Young Hwa, Yoo Nam Jin, Lee Sug Hyung
Department of Pathology, College of Medicine, The Catholic University of Korea, Seoul, Korea.
APMIS. 2007 Aug;115(8):900-5. doi: 10.1111/j.1600-0463.2007.apm_706.x.
FLASH was initially identified as a pro-apoptotic protein that transmits an apoptosis signal during death receptor-induced apoptosis. Additionally, diverse biologic roles of FLASH, including TNF-induced NF-kappaB activation, cell-cycle progression and cell division, have been identified. Although such functions are important in cancer pathogenesis, little is known about the alterations of FLASH gene and FLASH protein expression in human cancers. In this study, we analyzed the expression of FLASH protein in 60 gastric adenocarcinomas by immunohistochemistry. We furthermore analyzed mutation of FLASH in exon 8, where two polyadenine tracts ((A)8 and (A)9) are present, by single-strand conformation polymorphism (SSCP) assay in 184 gastric adenocarcinomas. By immunohistochemistry, FLASH protein expression in cancer cells was detected positively in 42 gastric carcinoma tissues (70%), whereas its expression in epithelial cells of normal gastric mucosa was shown as no or very weak intensity. Mutational analysis detected one FLASH mutation in the gastric carcinomas (0.5%). The increased expression of FLASH in the malignant gastric epithelial cells compared to the normal mucosal epithelial cells suggests that FLASH expression may play a role in gastric tumorigenesis. Also, the data suggest that somatic mutation of FLASH is a rare event in gastric carcinomas.
FLASH最初被鉴定为一种促凋亡蛋白，在死亡受体诱导的细胞凋亡过程中传递凋亡信号。此外，还发现了FLASH的多种生物学作用，包括肿瘤坏死因子诱导的核因子κB激活、细胞周期进程和细胞分裂。尽管这些功能在癌症发病机制中很重要，但对于人类癌症中FLASH基因和FLASH蛋白表达的改变却知之甚少。在本研究中，我们通过免疫组织化学分析了60例胃腺癌中FLASH蛋白的表达。此外，我们还通过单链构象多态性（SSCP）分析，对184例胃腺癌中存在两个多聚腺嘌呤序列（(A)8和(A)9）的第8外显子中的FLASH突变进行了分析。通过免疫组织化学，在42例胃癌组织（70%）中癌细胞中检测到FLASH蛋白表达呈阳性，而其在正常胃黏膜上皮细胞中的表达则显示为无或非常弱的强度。突变分析在胃癌中检测到1例FLASH突变（0.5%）。与正常黏膜上皮细胞相比，恶性胃上皮细胞中FLASH表达增加表明FLASH表达可能在胃肿瘤发生中起作用。此外，数据表明FLASH的体细胞突变在胃癌中是一种罕见事件。
