SH3GL2 基因通过调节喉癌细胞系 Hep2 中的 EGFR 部分参与 MEK-ERK 信号通路。
SH3GL2 gene participates in MEK-ERK signal pathway partly by regulating EGFR in the laryngeal carcinoma cell line Hep2.
机构信息
Department of Neurobiology, China Medical University, Shenyang, PR China.
出版信息
Med Sci Monit. 2010 Jun;16(6):BR168-73.
BACKGROUND
The human Src homology 3 (SH3) domain GRB2-like 2 (SH3GL2) gene, a novel tumor suppressor gene in laryngeal squamous cell carcinoma (LSCC), induces apoptosis of tumor cells by regulating intra-cellular signal transduction networks. The objective of this study was to investigate the molecular mechanism of SH3GL2 in laryngeal carcinogenesis.
MATERIAL/METHODS: RNA interference inhibited the expression of level of SH3GL, and RT-PCR and Western blotting were applied to evaluate the expression level of SH3GL2 after RNA interference. After RNA interference, flow cytometry and 3-(4,5-dimethyl-2-thiazolyl)-2, 5-diphenyl-2H-tetrazolium bromide (MTT) assay were used to detect the biological effects, and Western blotting was used to determine the expression of EGFR and phosphorylated ERK1/2. The Hep2 cells transfected with siRNA-SH3GL2 were treated by U0126 (selective MEK1/2 Inhibitor), and the phosphorylated ERK1/2 proteins were detected by Western blotting; cell proliferation and apoptosis were detected subsequently.
RESULTS
Our results show that the expression level of epidermal growth factor receptor (EGFR) and phosphorylated extracellular signal-regulated kinase 1/2 (ERK1/2) were up-regulated after down-regulation of SH3GL2. Additionally, SH3GL2 promoted apoptosis while decreasing cell proliferation. However, if ERK1/2 was inhibited by U0126, the apoptosis rate increased and proliferation decreased inversely.
CONCLUSIONS
SH3GL2 participates in the regulation of apoptosis through the MEK-ERK signal pathway by adjusting EGFR in the laryngeal carcinoma cell line Hep2.
背景
人类Src 同源结构域 3（SH3）域 GRB2 样 2（SH3GL2）基因是喉鳞状细胞癌（LSCC）中的一种新型肿瘤抑制基因，通过调节细胞内信号转导网络诱导肿瘤细胞凋亡。本研究旨在探讨 SH3GL2 在喉癌发生中的分子机制。
材料/方法：采用 RNA 干扰抑制 SH3GL 的表达，应用 RT-PCR 和 Western blot 检测 RNA 干扰后 SH3GL2 的表达水平。RNA 干扰后，采用流式细胞术和 3-(4,5-二甲基-2-噻唑基)-2,5-二苯基-2H-四唑溴盐（MTT）检测法检测生物效应，Western blot 检测 EGFR 和磷酸化 ERK1/2 的表达。将 siRNA-SH3GL2 转染的 Hep2 细胞用 U0126（选择性 MEK1/2 抑制剂）处理，Western blot 检测磷酸化 ERK1/2 蛋白；随后检测细胞增殖和凋亡。
结果
我们的结果表明，下调 SH3GL2 后，表皮生长因子受体（EGFR）和磷酸化细胞外信号调节激酶 1/2（ERK1/2）的表达水平上调。此外，SH3GL2 促进凋亡，同时降低细胞增殖。然而，如果用 U0126 抑制 ERK1/2，则凋亡率增加，增殖相反减少。
结论
SH3GL2 通过调节喉癌细胞系 Hep2 中的 EGFR，参与通过 MEK-ERK 信号通路调节凋亡。
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