Identification of a novel tumor transforming gene GAEC1 at 7q22 which encodes a nuclear protein and is frequently amplified and overexpressed in esophageal squamous cell carcinoma.
Identification of a novel tumor transforming gene GAEC1 at 7q22 which encodes a nuclear protein and is frequently amplified and overexpressed in esophageal squamous cell carcinoma.
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DOI：
10.1038/sj.onc.1210390
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发表时间：
2007-08-30
期刊：
影响因子：
8
通讯作者：
Tang, J. C. O.
中科院分区：
文献类型：
--
作者：
Law, F. B. F.;Chen, Y. W.;Wong, K. Y.;Ying, J.;Tao, Q.;Langford, C.;Lee, P. Y.;Law, S.;Cheung, R. W. L.;Chui, C. H.;Tsao, S. W.;Lam, K. Y.;Wong, J.;Srivastava, G.;Tang, J. C. O.
通过比较DNA指纹图谱，我们确定了一个357 bp的DNA片段经常在食管鳞状细胞癌（ESCC）扩增。该片段与映射到7 q22的表达序列标签重叠。进一步的5′端和3′端快速扩增表明，该基因是一个新的单外显子基因，全长2052 bp，编码109个氨基酸（~15 kDa）的核蛋白。该基因被命名为GAEC 1（Gene Amplified in Esophageal Cancer 1），在6/10个ESCC细胞系中通过高分辨率1-Mb阵列-CGH鉴定位于7q22.1的1-2 Mb扩增子内。GAEC 1在正常组织中广泛表达，包括食管和胃肠道器官;在6/10（60%）ESCC细胞系和34/99（34%）原发性肿瘤中扩增和过表达。GAEC 1在3 T3小鼠成纤维细胞中的过表达引起软琼脂中的病灶形成和集落形成，与H-ras相当，并且将GAEC 1转染的3 T3细胞注射到无胸腺裸鼠体内形成未分化肉瘤，表明GAEC 1是转化癌基因。虽然GAEC 1扩增与临床病理参数和预后之间没有显著相关性，但我们的研究表明，过表达的GAEC 1具有致瘤潜力，并表明过表达的GAEC 1可能在ESCC发病机制中发挥重要作用。
By comparative DNA fingerprinting, we identified a 357-bp DNA fragment frequently amplified in esophageal squamous cell carcinomas (ESCC). This fragment overlaps with an expressed sequence tag mapped to 7q22. Further 5′ and 3′-rapid amplification of cDNA ends revealed that it is part of a novel, single-exon gene with full-length mRNA of 2052-bp and encodes a nuclear protein of 109 amino acids (~15-kDa). This gene, designated as GAEC1 (Gene Amplified in Esophageal Cancer 1), was located within a 1-2 Mb amplicon at 7q22.1 identified by high-resolution 1-Mb array-CGH in 6/10 ESCC cell lines. GAEC1 was ubiquitously expressed in normal tissues including esophageal and gastrointestinal organs; with amplification and overexpression in 6/10 (60%) ESCC cell lines and 34/99 (34%) primary tumors. Overexpression of GAEC1 in 3T3 mouse fibroblasts caused foci formation and colony formation in soft agar, comparable to H-ras, and injection of GAEC1-transfected 3T3 cells into athymic nude mice formed undifferentiated sarcoma in vivo, indicating that GAEC1 is a transforming oncogene. Although no significant correlation was observed between GAEC1 amplification and clinicopathological parameters and prognosis, our study demonstrated that overexpressed GAEC1 has tumorigenic potential and suggest that overexpressed GAEC1 may play an important role in ESCC pathogenesis.
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