Expression of Rab5a in hepatocellular carcinoma: Possible involvement in epidermal growth factor signaling
Expression of Rab5a in hepatocellular carcinoma: Possible involvement in epidermal growth factor signaling
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DOI：
10.1111/j.1872-034x.2007.00143.x
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发表时间：
2007-11-01
影响因子：
4.2
通讯作者：
Hayashi, Norio
中科院分区：
文献类型：
--
作者：
Fukui, Koji;Tamura, Shinji;Hayashi, Norio
目的：Rab亚家族在细胞内转运中发挥作用。Rab 5a尤其参与受体介导的内吞作用。表皮生长因子（EGF）是已知的诱导细胞迁移和促进入侵和血管生成。表皮生长因子受体（EGFR）在加入表皮生长因子后被积极内化。本研究的目的是阐明Rab 5a在肝细胞癌（HCC）中的表达，并研究其对EGF signaling.Methods的影响：Rab 5a蛋白在HCC和相应的非肿瘤组织中的表达从23例HCC患者接受手术切除进行了免疫印迹分析。结果：23例肝癌组织中有15例（65.2%）Rab 5a蛋白高表达（肿瘤/非肿瘤（T/N）比值>= 1）。Rab 5a抗原在癌细胞的胞浆和胞膜中呈弥漫性表达。膜相关Rab 5a也通过HCC中的过表达而增强。PLC/PRF/5/Rab 5aDN细胞中EGF诱导的EGFR内吞和MAP激酶磷酸化被抑制。结论：HCC中Rab 5a的过表达可能在EGF信号转导中起重要作用。
Aim: The Rab subfamily plays a role in intracellular transport. Rab5a is, in particular, involved in receptor-mediated endocytosis. Epidermal growth factor (EGF) is known to induce cell migration and promote invasion and angiogenesis. The EGF receptor (EGFR) is actively internalized upon the addition of EGF. The aim of the present study was to clarify the expression of Rab5a in hepatocellular carcinomas (HCC) and to examine its effect on EGF signaling.Methods: The expression of the Rab5a protein in HCC and corresponding non-tumorous tissues from 23 patients with HCC who had undergone surgical resection were analyzed by immunoblotting. A stable transfectant of Rab5a dominant negative (S34N) was established in a human hepatoma cell line, PLC/PRF/5 (PLC/PRF/5/Rab5aDN).Results: High expression (tumor/non-tumor (T/N) ratios >= 1) of Rab5a protein in HCC compared to the paired non-tumortissues was recognized in 15 patients (65.2%) of 23 samples. The Rab5a antigen was diffusely expressed in the cytoplasm and membranes of the cancer cells. The membrane-associated Rab5a is also enhanced via overexpression in HCC. The EGF-induced endocytosis of EGFR and the phosphorylation of MAP kinase were inhibited in PLC/PRF/5/Rab5aDN cells. The migration of PLC/PRF/5/Rab5aDN cells induced by EGF was also significantly attenuated.Conclusions: These results indicate that the overexpression of Rab5a in HCC may play an important role in EGF signaling.