HCRP-1在人前列腺癌迁移、侵袭中的作用

The role of HCRP-1 in suppressing metastasis of human prostate cancer

[目的]研究HCRP-1基因在前列腺癌迁移和侵袭中的作用。[方法]通过免疫组化技术评估HCRP-1在前列腺癌发生发展过程中的作用;分别用siRNA-Ctrl和siRNA-HCRP-1转染人前列腺癌细胞系PC3和DUl45细胞;细胞迁移实验和细胞侵袭实验分别检测HCRP-1基因低表达对2种前列腺癌细胞迁移和侵袭能力的影响;利用Westem Blot检测HCRP-1基因低表达后对2种前列腺癌细胞中EGFR、ERK和基质金属蛋白酶-2(metalloproteinase-2,MMP-2)蛋白表达的影响。[结果]相比癌旁前列腺组织,HCRP-1在前列腺癌组织中异常低表达(t=5.614,P=0.001),且与Gleason评分、TNM分期有关(χ^(2)=8.750,P=0.031;χ^(2)=5.237,P=0.021;χ^(2)=6.537,P=0.010);低表达HCRP-1能增强前列腺癌细胞迁移和侵袭的能力(t=4.675,P=0.001);抑制HCRP-1表达致使活化的EGFR、ERK异常增加以及MMP-2上调(t=6.891,P=0.001;t=5.930,P=0.001;t=4.873,P=0.001),从而影响前列腺癌的转移。[结论]晚期前列腺癌组织和Gleason评分大于7分的患者中HCRP-1表达水平下降;抑制HCRP-1表达后,前列腺癌细胞的迁移和侵袭能力上升,且肿瘤细胞的EGFR、ERK、MMP-2表达上升。

[Objective]To investigate the role of HCRP-1 gene in the occurrence and development of prostate cancer(PCA)and explore its possible molecular mechanism.[Method]Immunohistochemical techniques(IHC)was used to determine the significance of HCRP-1 in PCA progression.The plasmid siRNA-Ctrl or siRNA-HCRP-1 was transfected into PC3 and DUl45 cells.Then the migration and invasion abilities in these cells were studied by performing cell migration and cell invasion assay.Western Blot was used to determine the protein expressions of EGFR,ERK and MMP-2 after knockdown of HCRP-1 in PCA cells.[Result]The expression of HCRP-1 in PCA tissues was significantly lower than in tumor adjacent normal prostate tissues(t=5.614,P=0.001).And reduced HCRP-1 staining was significantly correlated with Gleason score and TNM stage(χ^(2)=8.750,P=0.031;χ^(2)=5.237,P=0.021;χ^(2)=6.537,P=0.010).It can enhance the abilities of PCA cells to migrate and invade by knockdown expression of HCRP-1(t=4.675,P=0.001).Moreover,knockdown of HCRP-1 may promote the metastasis of PCA result from the abnormal increases of pEGFR and pERK,which could subsequently upregulate MMP-2 expression(t=6.891,P=0.001;t=5.930,P=0.001;t=4.873,P=0.001).[Conclusion]The expression of HCRP-1 decreased in advanced prostate cancer tissues and patients with Gleason score greater than 7;after inhibiting the expression of hcrp-1,the migration and invasion ability of prostate cancer cells increased,and the expression of EGFR,ERK and MMP-2 increased.