生长因子受体结合蛋白10(growth factor receptor-bound protein 10,GRB10)是GRB7信号转导家族成员,包含五个结构域,可与多种酪氨酸激酶受体和非酪氨酸激酶受体结合,在细胞信号转导中起重要作用。GRB10在胰岛素信号通路、PI3K/AKT/mTOR...生长因子受体结合蛋白10(growth factor receptor-bound protein 10,GRB10)是GRB7信号转导家族成员,包含五个结构域,可与多种酪氨酸激酶受体和非酪氨酸激酶受体结合,在细胞信号转导中起重要作用。GRB10在胰岛素信号通路、PI3K/AKT/mTOR等通路中既可抑制也可激活信号转导,具体作用取决于细胞类型和信号强度。此外,GRB10参与调节能量代谢、精神行为和神经发育等。GRB10在肿瘤中具有双重作用,调控机制可能与GRB10亚型差异、肿瘤细胞起源、基因突变背景及肿瘤微环境有关。本综述总结了GRB10的功能和作用机制,阐述了GRB10在肿瘤中的研究进展,旨在为临床治疗提供新思路。展开更多
To examine phosphatase and tensin homology deleted in chromosome 10 (PTEN),hypoxia-inducible factor-1 alpha (HIF-1 alpha) gene expressions and their relation to vascular endothelial growth factor(VEGF) protein express...To examine phosphatase and tensin homology deleted in chromosome 10 (PTEN),hypoxia-inducible factor-1 alpha (HIF-1 alpha) gene expressions and their relation to vascular endothelial growth factor(VEGF) protein expression in the patients with human colorectal adenomas and adenocarcinomas.Methods The expression of PTEN,HIF-1 alpha gene was detected by using in situ hybridization,and the VEGF expression levels by immunohistochemistry in colorectal adenomas and primary colorectal adenocarcinoma.Results Strong expression of HIF-1 alpha was detectable in the majority of colorectal dadenocarcinoma,particularly surrounding areas of necrosis in adenocarcinoma.PTEN,HIF-1 alpha mRNA and VEGF protein were positive in 51.6%,67.7% and 59.7% respectively in 62 cases of adenocarcinomas,and 77.8%,44.4% and 33.3% respectively in 18 cases of adenomas.The positive rate of VEGF was higher in the patients with colorectal adenocarcinomas than that in those with adenomas,whereas that of PTEN mRNA was contrary.HIF-1 mRNA expression was correlated significantly with lymph node metastasis,liver metastasis,Duke’s stage and recurrence.During colorectal tumor progression,the expression of HIF-1 alpha mRNA was positively correlated with the VEGF protein expression (χ2= 4.751 ,P<0.05),but negatively with the PTEN mRNA expression(χ2=21.84,P<0.01).Conclusion The absence or low expression of PTEN and the increased levels of HIF-1α and VEGF may paly an important role in carcinogenesis and progression of colorectal carcinoma.These results suggest that VEGF upregulated by HIF-1 alpha gene may be involved in angiogenesis of colorectal adenocarcinoma.4 refs,1 tab.展开更多
文摘生长因子受体结合蛋白10(growth factor receptor-bound protein 10,GRB10)是GRB7信号转导家族成员,包含五个结构域,可与多种酪氨酸激酶受体和非酪氨酸激酶受体结合,在细胞信号转导中起重要作用。GRB10在胰岛素信号通路、PI3K/AKT/mTOR等通路中既可抑制也可激活信号转导,具体作用取决于细胞类型和信号强度。此外,GRB10参与调节能量代谢、精神行为和神经发育等。GRB10在肿瘤中具有双重作用,调控机制可能与GRB10亚型差异、肿瘤细胞起源、基因突变背景及肿瘤微环境有关。本综述总结了GRB10的功能和作用机制,阐述了GRB10在肿瘤中的研究进展,旨在为临床治疗提供新思路。
文摘To examine phosphatase and tensin homology deleted in chromosome 10 (PTEN),hypoxia-inducible factor-1 alpha (HIF-1 alpha) gene expressions and their relation to vascular endothelial growth factor(VEGF) protein expression in the patients with human colorectal adenomas and adenocarcinomas.Methods The expression of PTEN,HIF-1 alpha gene was detected by using in situ hybridization,and the VEGF expression levels by immunohistochemistry in colorectal adenomas and primary colorectal adenocarcinoma.Results Strong expression of HIF-1 alpha was detectable in the majority of colorectal dadenocarcinoma,particularly surrounding areas of necrosis in adenocarcinoma.PTEN,HIF-1 alpha mRNA and VEGF protein were positive in 51.6%,67.7% and 59.7% respectively in 62 cases of adenocarcinomas,and 77.8%,44.4% and 33.3% respectively in 18 cases of adenomas.The positive rate of VEGF was higher in the patients with colorectal adenocarcinomas than that in those with adenomas,whereas that of PTEN mRNA was contrary.HIF-1 mRNA expression was correlated significantly with lymph node metastasis,liver metastasis,Duke’s stage and recurrence.During colorectal tumor progression,the expression of HIF-1 alpha mRNA was positively correlated with the VEGF protein expression (χ2= 4.751 ,P<0.05),but negatively with the PTEN mRNA expression(χ2=21.84,P<0.01).Conclusion The absence or low expression of PTEN and the increased levels of HIF-1α and VEGF may paly an important role in carcinogenesis and progression of colorectal carcinoma.These results suggest that VEGF upregulated by HIF-1 alpha gene may be involved in angiogenesis of colorectal adenocarcinoma.4 refs,1 tab.
