MGr1-Ag/37LRP promotes growth and proliferation of gastric cancer in vitro and in vivo

MGr1-Ag/37LRP promotes growth and proliferation of gastric cancer in vitro and in vivo
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MGr1-Ag/37LRP在体外和体内促进胃癌的生长和增殖

DOI:
10.1038/cgt.2014.36
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发表时间:
2014-07
影响因子:
6.4
通讯作者:
Zhang, H.
Zhang, H.
中科院分区:
医学3区
文献类型:
--
作者:
Wang, Y.;Zhang, N.;Zhang, H.;Zhang, H.

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胃癌是一种侵袭性肿瘤,预后差.我们以前报道过MGr 1-Ag参与胃癌的多药耐药和抗凋亡。然而,MGr 1-Ag在GC增殖中的确切功能尚不清楚。在本研究中,我们发现MGr 1-Ag在胃癌组织和四种胃癌细胞系中高表达,与非肿瘤胃组织或胃粘膜上皮细胞相比。胃癌组织中MGr 1-Ag/37 LRP的高表达也与胃癌患者中位生存期的缩短相一致。本研究采用慢病毒介导的RNA干扰技术,分别在胃癌细胞株SGC 7901和胃癌细胞株MKN 45中下调MGr 1-Ag的表达,观察其对胃癌细胞生长的影响。进一步的研究表明,MGr 1-Ag基因的敲低可抑制胃癌细胞的增殖,其机制可能是抑制胃癌细胞进入S期,诱导胃癌细胞凋亡。软琼脂集落形成实验表明,经小干扰RNA(siRNA)转染后,SGC 7901和MKN 45细胞的殖民地形成能力下降。Western blot结果显示,慢MGr siRNA转染胃癌细胞后,cyclin D1和Bcl-2表达下调,p27和Bax表达上调。进一步研究表明,MGr 1-Ag对胃癌细胞的增殖作用依赖于其层粘连蛋白结合区。综上所述,这些数据揭示了MGr 1-Ag的一种新功能,可能用作GC的独立预后因子和潜在的治疗靶点。
Gastric carcinoma (GC) is an aggressive cancer with a poor prognosis. We previously reported that MGr1-Ag was involved in multidrug resistance and anti-apoptosis in GC. However, the exact function of MGr1-Ag in GC proliferation is not clear. In this study, we found that MGr1-Ag was highly expressed in GC tissues and four GC cell lines compared with nontumor gastric tissues or gastric epithelial mucosa cells. The high expression of MGr1-Ag/37LRP was also consistent with the decreased median survival time of GC patients. We employed lenti-mediated RNA interference technique to knock down MGr1-Ag expression in SGC7901 and MKN45 cells, respectively, and observed its effects on GC cells growth in vitro and in vivo. Further study showed that knockdown of MGr1-Ag could inhibit GC cell proliferation by inhibiting the cell cycle S-phase entry and induced apoptosis. Soft agar colony formation assay indicated that the colony formation ability of SGC7901 and MKN45 cells decreased after lenti-MGr1-Ag small interfering RNA (siRNA) infection. Western blot revealed that cyclin D1 and Bcl-2 expression were downregulated whereas p27 and Bax were upregulated in lenti-MGr-siRNA-infected GC cells. Further study demonstrated that the proliferation effect of MGr1-Ag in GC is dependent on its laminin-binding region. Taken together, these data revealed a novel function of MGr1-Ag that can possibly be used as an independent prognostic factor and a potential therapeutic target for GC.
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发表时间: 1998
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胃癌中缺氧介导的 MGr1-Ag/37LRP 上调是通过缺氧诱导因子 1 依赖性机制发生的,并有助于耐药性。
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发表时间: 1997-12-01
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