Overexpression of carbonic anhydrase-related protein XI promotes proliferation and invasion of gastrointestinal stromal tumors
Overexpression of carbonic anhydrase-related protein XI promotes proliferation and invasion of gastrointestinal stromal tumors
复制标题
DOI：
10.1007/s00428-005-1225-3
复制
发表时间：
2005-07-01
期刊：
影响因子：
3.5
通讯作者：
Onishi, S
中科院分区：
文献类型：
--
作者：
Morimoto, K;Nishimori, I;Onishi, S
碳酸酐酶相关蛋白(CA-RP)的三种异构体在CA基因家族中进化上保守，但缺乏经典的CA活性。虽然CA-RPS的生物学功能尚不清楚，但已有报道在某些类型的肿瘤中过表达CA-RPVIII。基于CA-RP在神经细胞中普遍表达的结果，我们研究了三种CA-RP在胃肠道间质瘤中的表达。免疫组织化学分析显示，在22例胃肠道间质瘤组织中，13例(59%)和20例(91%)CA-RP蛋白在和XI的胞浆中均有表达，而在Cajal肠组织中均未检测到。CA-RPS VIII和XI的阳性信号在GIST的周边部比中央部更强，而CA-RPS X的表达在GIST中均未见明显信号。通过逆转录-聚合酶链式反应-Southern印迹和免疫细胞化学方法观察到CA-RPS在GIST-T1细胞中的表达模式。CA-RP XI在GIST-T1细胞中的异位表达在体外诱导细胞增殖和侵袭。提示CA-RP XI在GIST的发生发展中起一定作用。
Three isoforms of carbonic anhydrase-related protein (CA-RP) are evolutionally well conserved among the CA gene family but lack classical CA activity. Although the biological function of CA-RPs is unknown, overexpression of CA-RP VIII has been reported in certain tumor types. Based on the finding that CA-RPs are commonly expressed in the neuronal cells, we investigated expression of all three CA-RPs in gastrointestinal stromal tumor (GIST). In contrast to no detectable signal of any of the three CA-RPs in intestinal cells of Cajal, immunohistochemical analysis showed distinct cytoplasmic expressions of CA-RPs VIII and XI in 13 (59%) and 20 (91%) of 22 GIST tissue specimens, respectively. The positive signals for both CA-RPs VIII and XI were more intense in the periphery than in the central part of GISTs, whereas no significant signal for CA-RP X expression was observed in any of the GISTs. These expression patterns of CA-RPs were consistently observed by reverse transcription-polymerase chain reaction-Southern blot and immunocytochemistry in the cultured GIST cell line GIST-T1. Ectopic expression of CA-RP XI in GIST-T1 cells induced cell proliferation and invasion in vitro. These findings indicate that CA-RP XI plays a role in the development of GIST.