收稿日期: 2022-11-25
录用日期: 2023-03-15
网络出版日期: 2023-03-28
基金资助
上海市自然科学基金(22ZR1450000)
Expression of tetraspanin 1 in breast cancer and its mechanism in promoting the progression of breast cancer
Received date: 2022-11-25
Accepted date: 2023-03-15
Online published: 2023-03-28
Supported by
Natural Science Foundation of Shanghai(22ZR1450000)
目的·探究四次跨膜蛋白1(tetraspanin 1,TSPAN1)在乳腺癌中的表达,及其对乳腺癌细胞迁移、侵袭能力的影响。方法·使用免疫组织化学染色(immunohistochemistry staining,IHC)检测106例乳腺癌患者的癌组织及癌旁组织中TSPAN1的表达,并分析其与患者临床特征的相关性。利用癌症基因组图谱(The Cancer Genome Atlas,TCGA)数据库分析TSPAN1 mRNA在乳腺癌及癌旁组织中的表达,及其与患者临床特征的相关性。在乳腺癌细胞MDA-MB-231、SUM159PT中下调TSPAN1后,通过细胞划痕实验、细胞侵袭实验检测TSPAN1对上述细胞迁移、侵袭的影响,并采用蛋白质印迹法(Western blotting)检测细胞上皮-间质转化(epithelial-mesenchymal transition,EMT)相关蛋白(E-钙黏蛋白、N-钙黏蛋白和波形蛋白)的表达。结果·IHC的结果显示,TSPAN1在乳腺癌组织中的表达高于癌旁组织(P=0.000),且其表达水平与肿瘤的总TNM分期、M分期、N分期和病理学分级显著相关(均P<0.05)。对来自TCGA数据库的转录组测序数据分析的结果显示,TSPAN1 mRNA在乳腺癌组织中的表达高于癌旁组织(P=0.000),其在TNM Ⅲ~Ⅳ期的乳腺癌组织中的表达高于TNMⅠ~Ⅱ期(P=0.007)。与转染Control siRNA相比,转染TSPAN1 siRNA的MDA-MB-231和SUM159PT细胞的迁移、侵袭能力均有所下降,E-钙黏蛋白的表达增加、N-钙黏蛋白及波形蛋白的表达减少(均P<0.05)。结论·TSPAN1在乳腺癌组织中表达较高,可促进乳腺癌细胞的迁移和侵袭。
曹源 , 王红霞 , 朱灜 , 李军建 . 四次跨膜蛋白1在乳腺癌中的表达及其促进乳腺癌进展的作用机制[J]. 上海交通大学学报(医学版), 2023 , 43(3) : 293 -300 . DOI: 10.3969/j.issn.1674-8115.2023.03.004
Objective ·To investigate the expression of tetraspanin 1 (TSPAN1) in breast cancer and its effect on the migration and invasion of breast cancer cells. Methods ·Immunohistochemistry staining (IHC) was used to detect the expression of TSPAN1 in breast cancer tissues and para-tumor tissues from 106 clinical patients, and to analyze its correlation with the clinical characteristics of patients. The Cancer Genome Atlas (TCGA) database was used to analyze the expression of TSPAN1 mRNA in breast cancer tissues and para-tumor tissues, and its correlation with the clinical characteristics of patients. After down-regulation of TSPAN1 in breast cancer cells MDA-MB-231 and SUM159PT, the effects of TSPAN1 on migration and invasion of cells were detected by wound healing assay and transwell assay, and the expression of epithelial-mesenchymal transition (EMT)-related proteins (E-cadherin, N-cadherin and vimentin) were detected by Western blotting. Results ·IHC results showed that the expression of TSPAN1 in breast cancer tissues was higher than that in para-tumor tissues (P=0.000), and the expression of TSPAN1 in total TNM stages, M stages, N stages and pathological grades of breast cancer tissues showed statistically significant differences (all P<0.05). The results of transcriptome sequencing data from TCGA database showed that the expression of TSPAN1 mRNA in breast cancer tissues was higher than that in para-tumor tissues (P=0.000), and its expression in TNM Ⅲ?Ⅳ stages was higher than that in TNMⅠ?Ⅱ stages (P=0.007). After down-regulation of TSPAN1, the migration and invasion ability of MDA-MB-231 and SUM159PT cells were decreased, the expression of E-cadherin was increased and the expressions of N-cadherin and vimentin were decreased (all P<0.05). Conclusion ·TSPAN1 is highly expressed in breast cancer tissues, which can promote the migration and invasion of breast cancer cells.
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