整合酶相互作用蛋白 1 调控胃癌细胞的增殖、凋亡和侵袭。
Integrase interactor 1 regulates proliferation, apoptosis and invasion in gastric cancer cells.
机构信息
Department of General Surgery, the Fourth Affiliated Hospital of Hebei Medical University, Shijiazhuang, Hebei 050011, China.
出版信息
Chin Med J (Engl). 2012 Feb;125(3):527-32.
BACKGROUND
Integrase interactor 1 (INI1), which encodes a component of the ATP-dependent chromatin remodeling hSWI-SNF complex, has been identified as a tumor suppressor in many tumors. Nonetheless, the role of INI1 in gastric tumor progression is not known exactly. The aim of this research was to investigate the effect of INI1 in the carcinogenesis and progression of gastric cancer.
METHODS
Gastric tumor tissues with different differentiation levels from clinical gastric carcinoma samples and adjacent control normal tissues were taken. Expression levels of INI1 were detected by quantitative reverse transcriptation-polymerase chain reaction (RT-PCR) and Western blotting. Gastric cancer cell line SGC7901 was transfected with INI1 eukaryotic expressing vector INI1-GFP. Cell proliferation activities were assessed by MTT; cell count and cell cycle were detected by flow cytometry (FCM); cell apoptosis were measured by TUNEL and FCM; cell migration and invasiveness were evaluated by wound healing and transwell assays. Expression levels of INI1 and proliferation-related genes including p16, p21, cyclin D1 and cyclin A, apoptosis genes p53, B-cell non-Hodgkin lymphoma-2 (Bcl-2), Bcl-2-associated x protein (Bax) and caspase-3, and invasion-related genes including intercellular adhesion molecule 1 (ICAM1), matrix metalloproteinase 2 (MMP2), MMP9 and tissue inhibitor of matrix metalloproteinase 1 (TIMP1), were detected by quantitative RT-PCR and Western blotting.
RESULTS
INI1 expression levels were lower in gastric carcinoma compared with adjacent control normal tissues. Overexpression of INI1 in SGC7901 cells inhibited its proliferation and invasiveness, but increased anoikis and G(0)/G(1) cell number. INI1-GFP transfection upregulated expression of INI1 and proliferation related genes p16 and p21, apoptosis genes p53 and Bax, and invasion-related genes TIMP1; cyclin D1, cyclin A, Bcl2, ICAM1, MMP2 and MMP9 were downregulated, and there was no significant change in caspase 3 levels.
CONCLUSION
INI1 plays a key role in gastric carcinogenesis by affecting proliferation, apoptosis and invasion.
背景
整合酶相互作用因子 1（INI1）编码 ATP 依赖性染色质重塑 hSWI-SNF 复合物的一个组成部分，已被鉴定为许多肿瘤中的肿瘤抑制因子。然而，INI1 在胃肿瘤进展中的作用尚不完全清楚。本研究旨在探讨 INI1 在胃癌发生和进展中的作用。
方法
从临床胃癌样本和相邻对照正常组织中获取不同分化程度的胃肿瘤组织。通过定量逆转录-聚合酶链反应（RT-PCR）和 Western blot 检测 INI1 的表达水平。将 INI1 真核表达载体 INI1-GFP 转染至胃癌细胞系 SGC7901 中。通过 MTT 评估细胞增殖活性；通过流式细胞术（FCM）检测细胞计数和细胞周期；通过 TUNEL 和 FCM 检测细胞凋亡；通过划痕愈合和 Transwell 测定评估细胞迁移和侵袭能力。通过定量 RT-PCR 和 Western blot 检测 INI1 和增殖相关基因（包括 p16、p21、cyclin D1 和 cyclin A）、凋亡基因（包括 p53、B 细胞非霍奇金淋巴瘤-2（Bcl-2）、Bcl-2 相关 X 蛋白（Bax）和半胱天冬酶-3）以及侵袭相关基因（包括细胞间黏附分子 1（ICAM1）、基质金属蛋白酶 2（MMP2）、MMP9 和基质金属蛋白酶组织抑制剂 1（TIMP1））的表达水平。
结果
与相邻对照正常组织相比，胃癌组织中 INI1 的表达水平较低。SGC7901 细胞中 INI1 的过表达抑制其增殖和侵袭，但增加了 anoikis 和 G0/G1 细胞数量。INI1-GFP 转染上调了 INI1 和增殖相关基因 p16 和 p21、凋亡基因 p53 和 Bax 以及侵袭相关基因 TIMP1 的表达；下调了 cyclin D1、cyclin A、Bcl2、ICAM1、MMP2 和 MMP9，caspase 3 水平无明显变化。
结论
INI1 通过影响增殖、凋亡和侵袭在胃癌发生中发挥关键作用。
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