The adenocarcinoma-associated antigen, AGR2, promotes tumor growth, cell migration, and cellular transformation
The adenocarcinoma-associated antigen, AGR2, promotes tumor growth, cell migration, and cellular transformation
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DOI：
10.1158/0008-5472.can-07-2930
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发表时间：
2008-01-15
期刊：
影响因子：
11.2
通讯作者：
Lowe, Anson W.
中科院分区：
文献类型：
--
作者：
Wang, Zheng;Hao, Ying;Lowe, Anson W.
AGR2 基因编码一种分泌蛋白，该蛋白在食道、胰腺、乳腺癌和前列腺癌中高度表达。本研究通过筛选细胞转化和肿瘤生长的成熟体外和体内测定法探讨了 AGR2 表达的影响。 RNA 干扰可降低 SEG-1 食管腺癌细胞中 AGR2 的表达。使用稳定转染后表达 AGR2 的 NIH3T3 细胞检查细胞转化。在体外对细胞系进行了密度依赖性和贴壁依赖性生长测定，并在体内作为裸鼠的肿瘤异种移植物进行了研究。 AGR2 表达减少的 SEG-1 细胞显示，贴壁独立集落生长减少 82%，肿瘤异种移植物大小减少 60%。表达 AGR2 的 NIH3T3 细胞的体外测定显示，病灶形成和贴壁依赖性生长增强。在体内，表达 AGR2 的 NIH3T3 细胞在裸鼠体内形成肿瘤。因此，AGR2表达促进食管腺癌细胞中的肿瘤生长，并且能够转化NIH3T3细胞。正常小鼠肠道的免疫组织化学检测到分泌谱系的增殖和分化肠细胞中 AGR2 的表达。 AGR2可能对肠道以及食管腺癌的生长和发育很重要。
The AGR2 gene encodes a secretory protein that is highly expressed in adenocarcinomas of the esophagus, pancreas, breast, and prostate. This study explores the effect of AGR2 expression with well-established in vitro and in vivo assays that screen for cellular transformation and tumor growth. AGR2 expression in SEG-1 esophageal adenocarcinoma cells was reduced with RNA interference. Cellular transformation was examined using NIH3T3 cells that express AGR2 after stable transfection. The cell lines were studied in vitro with assays for density-dependent and anchorage-independent growth, and in vivo as tumor xenografts in nude mice. SEG-1 cells with reduced AGR2 expression showed an 82% decrease in anchorage-independent colony growth and a 60% reduction in tumor xenograft size. In vitro assays of AGR2-expressing NIH3T3 cells displayed enhanced foci formation and anchorage-independent growth. In vivo, AGR2-expressing NIH3T3 cells established tumors in nude mice. Thus, AGR2 expression promotes tumor growth in esophageal adenocarcinoma cells and is able to transform NIH3T3 cells. Immunohistochemistry of the normal mouse intestine detected AGR2 expression in proliferating and differentiated intestinal cells of secretory lineage. AGR2 may be important for the growth and development of the intestine as well as esophageal adenocarcinomas.