BTG1 expression correlates with pathogenesis, aggressive behaviors and prognosis of gastric cancer: a potential target for gene therapy.
BTG1 expression correlates with pathogenesis, aggressive behaviors and prognosis of gastric cancer: a potential target for gene therapy.
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BTG1表达与胃癌的发病机制、侵袭行为和预后相关：基因治疗的潜在靶点
DOI：
10.18632/oncotarget.4081
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发表时间：
2015-08-14
期刊：
影响因子：
--
通讯作者：
Gou WF
中科院分区：
文献类型：
--
作者：
Zheng HC;Li J;Shen DF;Yang XF;Zhao S;Wu YZ;Takano Y;Sun HZ;Su RJ;Luo JS;Gou WF
我们发现BTG 1过表达抑制BGC-823和MKN 28细胞的增殖、迁移和侵袭，诱导G2/M期阻滞、分化、衰老和凋亡（p < 0.05）。BTG 1转染组Cyclin D1和Bax mRNA表达高于对照组和mock组，而cdc 2、p21、mTOR和MMP-9 mRNA表达低于对照组和mock组（p < 0.05）。经顺铂、MG 132、紫杉醇和SAHA处理后，两种BTG 1转染细胞的mRNA活性均低于对照组，凋亡率高于对照组，且呈时间和剂量依赖性（p < 0.05），同时耐药相关基因slug、CD 147、GRP 78、GRP 94、FBXW 7、TOP 1、TOP 2和GST-π表达降低。胃癌细胞经5-氮-2 ′-脱氧胞苷处理后，BTG 1表达恢复。BTG 1在胃癌中的表达明显低于非肿瘤性黏膜和淋巴结转移癌（p < 0.05）。BTG 1表达与胃癌浸润深度、淋巴结和静脉浸润、淋巴结转移、TNM分期及预后不良呈正相关（p < 0.05）。BTG 1在弥漫型胃癌中的表达明显低于肠型和混合型胃癌（p < 0.05）。在异种移植模型中，BTG 1过表达通过抑制增殖、增强自噬和凋亡抑制胃癌细胞的生长和肺转移。提示BTG 1基因表达下调可能与其启动子甲基化有关。BTG 1过表达可能逆转胃癌的侵袭性表型，并可能成为胃癌基因治疗的潜在靶点。
Here, we found that BTG1 overexpression inhibited proliferation, migration and invasion, induced G2/M arrest, differentiation, senescence and apoptosis in BGC-823 and MKN28 cells (p < 0.05). BTG1 transfectants showed a higher mRNA expression of Cyclin D1 and Bax, but a lower mRNA expression of cdc2, p21, mTOR and MMP-9 than the control and mock (p < 0.05). After treated with cisplatin, MG132, paclitaxel and SAHA, both BTG1 transfectants showed lower mRNA viability and higher apoptosis than the control in both time- and dose-dependent manners (p < 0.05) with the hypoexpression of chemoresistance-related genes (slug, CD147, GRP78, GRP94, FBXW7 TOP1, TOP2 and GST-π). BTG1 expression was restored after 5-aza-2′-deoxycytidine treatment in gastric cancer cells. BTG1 expression was statistically lower in gastric cancer than non-neoplastic mucosa and metastatic cancer in lymph node (p < 0.05). BTG1 expression was positively correlated with depth of invasion, lymphatic and venous invasion, lymph node metastasis, TNM staging and worse prognosis (p < 0.05). The diffuse-type carcinoma showed less BTG1 expression than intestinal- and mixed-type ones (p < 0.05). BTG1 overexpression suppressed tumor growth and lung metastasis of gastric cancer cells by inhibiting proliferation, enhancing autophagy and apoptosis in xenograft models. It was suggested that down-regulated BTG1 expression might promote gastric carcinogenesis partially due to its promoter methylation. BTG1 overexpression might reverse the aggressive phenotypes and be employed as a potential target for gene therapy of gastric cancer.