Downregulation of gastrokine-1 in gastric cancer tissues and restoration of its expression induced gastric cancer cells to apoptosis.
Downregulation of gastrokine-1 in gastric cancer tissues and restoration of its expression induced gastric cancer cells to apoptosis.
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胃癌组织中gastrokine-1的下调及其表达恢复诱导胃癌细胞凋亡
DOI：
10.1186/1756-9966-31-49
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发表时间：
2012-05-23
期刊：
影响因子：
--
通讯作者：
Chen MH
中科院分区：
文献类型：
--
作者：
Mao W;Chen J;Peng TL;Yin XF;Chen LZ;Chen MH
研究背景Gastrokine-1（GKN1）是一种分泌蛋白，在胃粘膜中特异性表达，以保护和维持胃上皮的完整性。本研究探讨GKN1在正常、癌前、癌变胃组织中的差异表达，探讨GKN1蛋白在胃癌细胞中的生物学功能。方法采用RT-PCR、Western blot、免疫组化法检测GKN1在正常、癌前、癌变胃组织及7种胃癌细胞系中的表达情况。基因转染用于恢复胃癌AGS细胞中GKN1的表达。检测转染细胞的表型变化（即细胞活力、细胞凋亡、细胞周期调节和胃癌细胞对氟尿嘧啶 (5-FU) 的敏感性）。采用DNA芯片分析凋亡相关基因的表达变化。结果7种胃癌细胞系中GKN1表达显着下调或缺失，且从正常粘膜、癌前组织到癌组织GKN1表达逐渐降低。此外，GKN1表达的恢复抑制了胃癌细胞的活力并诱导细胞凋亡。 GKN1 表达还增强了肿瘤细胞对 5-FU 治疗的敏感性。此外，还发现AGS细胞中GKN1的表达可调节19个凋亡相关基因的表达。结论GKN1的表达从正常粘膜、癌前组织到癌变胃组织中逐渐丧失，而GKN1表达的恢复则诱导胃癌细胞发生凋亡，并增强胃癌细胞对5-FU诱导的细胞凋亡的敏感性。
BackgroundGastrokine-1 (GKN1), a secreted protein, is specifically expressed in gastric mucosa to protect and maintain the integrity of gastric epithelium. The present study investigated differential expression of GKN1 in normal, precancerous, and cancerous gastric tissues, and explored the biological functions of GKN1 protein in gastric cancer cells.MethodsRT-PCR, Western blot, and immunohistochemistry were performed to detect GKN1 expression in normal, precancerous, cancerous gastric tissues and seven gastric cancer cell lines. Gene transfection was used to restore GKN1 expression in gastric cancer AGS cells. Phenotypic changes (i.e., cell viability, apoptosis, cell cycle modulation, and sensitivity of gastric cancer cells to fluorouracil (5-FU)) were assayed in the transfected cells. DNA microarrays were used to analyze expression changes of apoptosis-related genes.ResultsSignificant downregulation or absence of GKN1 expression in seven gastric cancer cell lines were detected and progressive decrease of GKN1 expression from normal mucosa, precancerous tissue, to cancer tissues was observed. Moreover, restoration of GKN1 expression suppressed gastric cancer cell viability and induced the cells to undergo apoptosis. GKN1 expression also enhanced tumor cell sensitivity to 5-FU treatment. Moreover, it was found that GKN1 expression in AGS cells modulated expression of 19 apoptosis-related genes.ConclusionsExpression of GKN1 is progressively lost from normal mucosa, precancerous to cancerous gastric tissues, while restoration of GKN1 expression induces gastric cancer cells to undergo apoptosis, and enhances sensitivity of gastric cancer cells to 5-FU-induced apoptosis.
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DOI：
10.1111/j.1349-7006.2000.tb00967.x
发表时间：
2000-05
期刊：
Japanese journal of cancer research : Gann
影响因子：
--
作者：
Yoshikawa Y;Mukai H;Hino F;Asada K;Kato I
通讯作者：
Kato I
影响因子：
2.3
作者：
Krejs, Guenter J.
通讯作者：
Krejs, Guenter J.
影响因子：
7.6
作者：
Martin, G.;Wex, T.;Nardone, G.
通讯作者：
Nardone, G.
影响因子：
3.6
作者：
Nardone, Gerardo;Martin, Giovanni;Arcari, Paolo
通讯作者：
Arcari, Paolo
影响因子：
24.5
作者：
Xing, Rui;Li, Wenmei;Lu, Youyong
通讯作者：
Lu, Youyong