Dopamine and cAMP regulated phosphoprotein MW 32 kDa is overexpressed in early stages of gastric tumorigenesis.
Dopamine and cAMP regulated phosphoprotein MW 32 kDa is overexpressed in early stages of gastric tumorigenesis.
复制标题
DOI：
10.1016/j.surg.2010.05.011
复制
发表时间：
2010-08
期刊：
影响因子：
3.8
通讯作者：
El-Rifai, Wael
中科院分区：
文献类型：
--
作者：
Mukherjee, Kaushik;Peng, Dunfa;Brifkani, Zaid;Belkhiri, Abbes;Pera, Manuel;Koyama, Tatsuki;Koehler, Elizabeth A. S.;Revetta, Frank L.;Washington, Mary K.;El-Rifai, Wael
胃腺癌是癌症死亡的主要原因。DARPP-32过表达在胃肿瘤发生级联中的作用仍不清楚。采用免疫组化方法检测533例乳腺癌组织中DARPP-32的表达。使用NIH 3 T3、AGS和SNU 16细胞研究DARPP-32在细胞转化和分子信号传导中的贡献。根据免疫染色模式计算的复合表达评分（CES）从正常或胃炎到化生、异型增生和腺癌显著增加（p<0.001）。在正常胃或胃炎和肿瘤样本的患者中，肿瘤中CES较高的可能性分别为76%和77%（p<0.001）。高中位数CES与高分化或中分化（p=0.03）胃腺癌相关。与对照相比，用DARPP-32转染的NIH 3 T3细胞表现出磷酸化AKT水平的增加和病灶数量的五倍增加（p =0.02）。DARPP-32在AGS细胞中的表达导致磷酸化AKT和BCL-2的蛋白水平增加。为了验证，使用shRNA敲低SNU 16细胞中的内源DARPP-32表达导致磷酸化AKT磷酸化和BCL-2水平降低。我们的研究结果表明DARPP-32过表达可能参与肠上皮化生的转变和肿瘤的进展。DARPP-32转化NIH 3 T3细胞并调节AKT和BCL-2的能力强调了其可能的致癌潜力。
Gastric adenocarcinoma is a leading cause of cancer mortality. The role of DARPP-32 overexpression in the gastric tumorigenesis cascade remains unclear. The expression of DARPP-32 in the multi-step carcinogenesis cascade was examined using immunohistochemistry analysis on 533 samples. The contribution of DARPP-32 in cellular transformation and molecular signaling was investigated using NIH3T3, AGS, and SNU16 cells. The composite expression score (CES), calculated from immunostaining patterns, increased significantly from normal or gastritis to metaplasia, dysplasia, and adenocarcinoma (p<0.001). In patients with normal stomach or gastritis and tumor samples, there was a 76% and 77% chance respectively (p<0.001) that CES was higher in the tumor. High median CES correlated with well- or moderately-differentiated (p=0.03) gastric adenocarcinomas. NIH3T3 cells transfected with DARPP-32 demonstrated increased levels of phospho-AKT and a five-fold increase in the number of foci as compared to control (p =0.02). DARPP-32 expression in AGS cells led to increased protein levels of phospho-AKT and BCL-2. For validation, the knockdown of endogenous DARPP-32 expression in SNU16 cells using shRNA resulted in decreased levels of phospho-AKT phosphorylation and BCL-2. Our results suggest that DARPP-32 overexpression may participate in transition to intestinal metaplasia and progression to neoplasia. The ability of DARPP-32 to transform NIH3T3 cells and regulate AKT and BCL-2 underscores its possible oncogenic potential.
登录
查看更多内容
影响因子：
3.7
作者：
Gu L;Waliany S;Kane SE
通讯作者：
Kane SE
影响因子：
11.2
作者：
Belkhiri, A;Zaika, A;El-Rifai, W
通讯作者：
El-Rifai, W
影响因子：
6
作者：
Leung, WK;Kim, JJ;Sepulveda, AR
通讯作者：
Sepulveda, AR
影响因子：
9.7
作者：
Norsett, KG;Lægreid, A;Sandvik, AK
通讯作者：
Sandvik, AK
影响因子：
254.7
作者：
Parkin, DM;Bray, F;Pisani, P
通讯作者：
Pisani, P