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纸质出版:2014
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胰十二指肠同源基因1在胃癌中的表达及对胃癌生物学 行为的影响[J]. 中山大学学报(医学科学版), 2014,35(2).
Expression of Pancreatic Duodenal Homeobox1 Gene and Its Effects on Cell Biological Behavior in Gastric Cancer[J]. Journal of Sun Yat-sen University (Medical Sciences), 2014, 35(2).
【目的】 明确PDX1基因在胃癌中的表达模式
探讨PDX1表达上调对胃癌细胞增殖和凋亡的影响
从而揭示PDX1在胃癌发生发展中的作用?【方法】 免疫组化法检测胃癌组织芯片的PDX1蛋白表达
RT-PCR和免疫印迹法检测3株胃癌细胞(AGS?SGC7901?BCG823)PDX1 mRNA表达;构建PDX1正义表达载体
瞬时转染胃癌细胞
免疫印迹法检测转染后PDX1?Ki-67?PCNA?Caspase3的表达
同时检测转染后胃癌细胞的增殖指数和凋亡指数?筛选PDX1稳定表达株
评价胃癌细胞伤口愈合?克隆形成?移植瘤形成等生物学行为?【结果】 胃癌组织芯片包括171例腺癌
12例黏液腺癌
6例印戒细胞癌
5例未分化癌
7例恶性间质瘤
1例类癌
8例正常胃黏膜组织?PDX1蛋白在正常胃粘膜组织中腺上皮细胞的胞浆及胞核中高表达
胃癌组织中PDX1蛋白则表达下降甚至缺失(P < 0.05);肿瘤分化级别越高
PDX1表达随之下降(P < 0.05);与淋巴结无转移组比较
淋巴结转移组PDX1表达显著降低(P < 0.05)?与正常对照相比
PDX1 mRNA和蛋白在胃癌细胞中表达微弱?瞬时转染PDX1正义表达载体后
PDX1表达明显上调
胃癌细胞增殖相关蛋白Ki67和PCNA下降
增殖指数显著下降;凋亡蛋白Caspase3被激活
cleaved- Caspase3被诱导表达
凋亡指数显著增加?与空质粒对照组比较
PDX1稳定过表达抑制了体外胃癌细胞的伤口愈合率以及克隆形成率和体内裸鼠移植瘤形成率(P < 0.05)? 【结论】 PDX1基因在胃癌组织和细胞中表达下调
与癌组织淋巴结转移与分化程度有关;PDX1基因可能在胃癌发展过程中可能起着重要作用?
【Objectives】 To determine PDX1 gene expression in gastric malignant and the influence of PDX1 upregulation in proliferation and apoptosis of gastric cancer cells. 【Methods】 Gastric cancerous tissue chips were used for detecting PDX1 protein expression by immunohistochemical staining. Three gastric cancer cell lines (AGS
SGC7901
BCG823) were used for detecting PDX1 mRNA and protein level by RT-PCR and Western blotting. Using gastric cancer cells in vitro
effects of PDX1 on cell proliferation and apoptosis after transient transfection with PDX1 vector as well as clone formation and wound healing after stable transfection were assessed. Using xenograft mice in vivo
tumor formation was evaluated. 【Results】 The gastric malignant chip includes 171 adenocarcinomas
12 mucinous adenocarcinoma
6 signet cell cancers
5 undiffernetiated carcinomas
7 malignant stromal tumors
1carcinoid and 8 gastric normal tissues. PDX1 protein was positive in plasma and nuclear of the normal gastric gland cells while absent or significantly down-regulated in gastric cancer (P < 0.05). Compared with normal control
PDX1 mRNA and protein level were also weakly in gastric cancer cell lines. After transient transfection
Ki67 and PCNA were decreased and cleaved-Caspase3 was induced following by PDX1 gene over-expression. Meanwhile
the proliferation index was decreased for 48 hours after transfection and the apoptotic index was increased for 24 hours after transfection. PDX1 overexpression significantly decreased the rates of wound healing
colonal formation and xenotransplanted tumor formation (P < 0.05). 【Conclusion】 This study implies that PDX1 gene is down-regulated in gastric cancerous tissues and cells and is associated with lymphatic metastasis and differentiation. Up-regulation of PDX1 gene inhibits gastric carcinogenesis.
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