大肠癌中PARG与β-catenin、MT1-MMP关系的研究
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摘要
目的:初步探讨大肠癌中PARG与β-catenin、MT1-MMP的表达意义及相互关系。
方法:1.制作人大肠腺瘤-腺癌组织芯片,采用免疫组化SP法检测PARG、PARP与NF-κB、β-catenin、MT1-MMP表达;
2.以PARP抑制剂5-AIQ为处理因素,采用Western Blot检测人大肠癌lovo细胞中PARG、PARP、NF-κB、β-catenin、MT1-MMP表达变化,并采用免疫荧光观察β-catenin表达部位。
3.以PARG抑制剂GLTN为处理因素,采用Western Blot检测人大肠癌lovo细胞中PARG、PARP、NF-κB、β-catenin、MT1-MMP表达变化。
结果:1. PARG、PARP和NF-κB在正常大肠黏膜和腺瘤组织中低表达,在腺癌组织中高表达,差别具有统计学意义(P<0.05);β-catenin在正常大肠黏膜和腺瘤组织表达于细胞膜上,在腺癌组织异常表达于细胞浆和/或细胞核,其异常表达率较正常黏膜和腺瘤显著增高,差别具有统计学意义(P<0.05);MT1-MMP在正常大肠黏膜组织和腺瘤组织无表达,在腺癌组织高表达,差别具有统计学意义(P<0.05)。在腺癌组织中,PARG、PARP、NF-κB、β-catenin、MT1-MMP表达与癌细胞浸润深度、淋巴结转移、Dukes分期有关;与肿瘤患者年龄、性别、肿瘤部位、肿瘤大小、分化程度无相关性。腺癌组织中PARG表达与NF-κB、β-catenin、MT1-MMP表达具有相关性(r分别为0.332,0.274,0.216,P值均<0.05 ),PARP表达与NF-κB、β-catenin、MT1-MMP表达具有相关性(r分别为0.398,0.291,0.227,P值均<0.05)。
2. PARP抑制剂5-AIQ作用于人大肠癌lovo细胞后, Western Blot检测显示PARG表达无明显改变(P>0.05),PARP、NF-κB、β-catenin、MT1-MMP表达降低,分别与5-AIQ未处理组比较,差异均具有统计学意义(P<0.05);免疫荧光检测β-catenin表达部位,其异常表达于胞浆、胞核。
3. PARG抑制剂GLTN作用于人大肠癌lovo细胞后, Western Blot检测显示PARG表达降低,PARP、NF-κB、β-catenin、MT1-MMP表达也降低,分别与GLTN未处理组比较,差异均具有统计学意义(P<0.05)。
结论:人大肠癌组织中PARG表达与β-catenin、MT1-MMP、NF-κB表达有关,PARG,PARP、NF-κB、β-catenin和MT1-MMP的表达与大肠癌发生发展关系密切。在大肠癌中,PARG可能通过调节PARP对β-catenin、NF-κB、MT1-MMP进行调节。
OBJECTIVE: To investigate the relationship of Poly(ADP-ribose) glycohydrolase (PARG) withβ-catenin and membrane type 1 matrix metalloproteinase (MT1-MMP) in human colorectal carcinoma .
METHODS:1. Immunohistochemical staining for PARG, PARP, NF-κB,β-catenin and MT1-MMP were carried out on colorectal adenoma-carcinoma tissue microarrays.
2. The expressions of PARG, PARP, NF-κB,β-catenin and MT1-MMP were detected by Western Blot in the 5-AIQ–treated and 5-AIQ–untreated lovo cells. The site ofβ-catenin expression in the cells was detected by immunofluorescence in both 5-AIQ- treated and 5-AIQ–untreated lovo cells. 5-AIQ was served as PARP inhibitor.
3.The expressions of PARG, PARP, NF-κB,β-catenin and MT1-MMP were detected by Western Blot in the GLTN–treated and GLTN–untreated lovo cells. GLTN was served as PARG inhibitor.
RESULTS: 1.PARG, PARP, NF-κB, expressions in adenocarcinoma were significantly higher than those in normal colorectal mucosa and adenoma(P<0.05). Expression ofβ-catenin was detected on the cell membrane in normal colorectal mucosa and adenoma, whereas in adenocarcinoma it was found in cytoplasmic and/or nuclear region(P<0.05). Moreover, the rate of abnormalβ-catenin expression was higher in adenocarcinoma compared to both normal colorectal mucosa and adenoma(P<0.05). Expression of MT1-MMP in normal colorectal mucosa and adenoma was negative, while the expression in adenocarcinoma was positive,(P<0.05). The expressions of PARG, PARP, NF-κB,β-catenin and MT1-MMP in adenocarcinoma showed a positive association with the depth of invasion, lymphatic metastasis and Duke’s stage (all P<0.05);Nevertheless, the above expression had no correlation at all with sex, age, site, size or differentiation (all P>0.05). PARG expression shows a positive correlation with the expressions ofβ-catenin , MT1-MMPand NF-κB ((r=0.274, 0.216, 0.332, P<0.05) respectively, while PARP expression shows a positive correlation with the expressions ofβ-catenin , MT1-MMP and NF-κB(r=0.291,0.027, 0.398,P<0.05) respectively。
2.The expressions of PARP, NF-κB,β-catenin and MT1-MMP detected by western blot in 5-AIQ-treated lovo cells were weaker than those in 5-AIQ-untreated lovo cells(P<0.05),however PARG expression wasn’t changed obviously(P>0.05). By immunofluorescence method, the expression ofβ-catenin was in cytolymph and/or in nucleus.
3.The expressions of PARG, PARP, NF-κB,β-catenin and MT1-MMP detected by western blot in GLTN-treated lovo cells were weaker than those in GLTN-untreated lovo cells(P<0.05).
CONCLUSION: The expression of PARG related to the expression of PARP, NF-κB,β-catenin and MT1-MMP in colorectal carcinoma. The expression of PARG, PARP, NF-κB,β-catenin and MT1-MMP were probably related to the development of colorectal carcinoma. PARG maybe playing an important roles in the regulation of NF- B,β-catenin and MT1-MMP expressions in colorectal carcinoma through regulation of PARP.
方法:1.制作人大肠腺瘤-腺癌组织芯片,采用免疫组化SP法检测PARG、PARP与NF-κB、β-catenin、MT1-MMP表达;
2.以PARP抑制剂5-AIQ为处理因素,采用Western Blot检测人大肠癌lovo细胞中PARG、PARP、NF-κB、β-catenin、MT1-MMP表达变化,并采用免疫荧光观察β-catenin表达部位。
3.以PARG抑制剂GLTN为处理因素,采用Western Blot检测人大肠癌lovo细胞中PARG、PARP、NF-κB、β-catenin、MT1-MMP表达变化。
结果:1. PARG、PARP和NF-κB在正常大肠黏膜和腺瘤组织中低表达,在腺癌组织中高表达,差别具有统计学意义(P<0.05);β-catenin在正常大肠黏膜和腺瘤组织表达于细胞膜上,在腺癌组织异常表达于细胞浆和/或细胞核,其异常表达率较正常黏膜和腺瘤显著增高,差别具有统计学意义(P<0.05);MT1-MMP在正常大肠黏膜组织和腺瘤组织无表达,在腺癌组织高表达,差别具有统计学意义(P<0.05)。在腺癌组织中,PARG、PARP、NF-κB、β-catenin、MT1-MMP表达与癌细胞浸润深度、淋巴结转移、Dukes分期有关;与肿瘤患者年龄、性别、肿瘤部位、肿瘤大小、分化程度无相关性。腺癌组织中PARG表达与NF-κB、β-catenin、MT1-MMP表达具有相关性(r分别为0.332,0.274,0.216,P值均<0.05 ),PARP表达与NF-κB、β-catenin、MT1-MMP表达具有相关性(r分别为0.398,0.291,0.227,P值均<0.05)。
2. PARP抑制剂5-AIQ作用于人大肠癌lovo细胞后, Western Blot检测显示PARG表达无明显改变(P>0.05),PARP、NF-κB、β-catenin、MT1-MMP表达降低,分别与5-AIQ未处理组比较,差异均具有统计学意义(P<0.05);免疫荧光检测β-catenin表达部位,其异常表达于胞浆、胞核。
3. PARG抑制剂GLTN作用于人大肠癌lovo细胞后, Western Blot检测显示PARG表达降低,PARP、NF-κB、β-catenin、MT1-MMP表达也降低,分别与GLTN未处理组比较,差异均具有统计学意义(P<0.05)。
结论:人大肠癌组织中PARG表达与β-catenin、MT1-MMP、NF-κB表达有关,PARG,PARP、NF-κB、β-catenin和MT1-MMP的表达与大肠癌发生发展关系密切。在大肠癌中,PARG可能通过调节PARP对β-catenin、NF-κB、MT1-MMP进行调节。
OBJECTIVE: To investigate the relationship of Poly(ADP-ribose) glycohydrolase (PARG) withβ-catenin and membrane type 1 matrix metalloproteinase (MT1-MMP) in human colorectal carcinoma .
METHODS:1. Immunohistochemical staining for PARG, PARP, NF-κB,β-catenin and MT1-MMP were carried out on colorectal adenoma-carcinoma tissue microarrays.
2. The expressions of PARG, PARP, NF-κB,β-catenin and MT1-MMP were detected by Western Blot in the 5-AIQ–treated and 5-AIQ–untreated lovo cells. The site ofβ-catenin expression in the cells was detected by immunofluorescence in both 5-AIQ- treated and 5-AIQ–untreated lovo cells. 5-AIQ was served as PARP inhibitor.
3.The expressions of PARG, PARP, NF-κB,β-catenin and MT1-MMP were detected by Western Blot in the GLTN–treated and GLTN–untreated lovo cells. GLTN was served as PARG inhibitor.
RESULTS: 1.PARG, PARP, NF-κB, expressions in adenocarcinoma were significantly higher than those in normal colorectal mucosa and adenoma(P<0.05). Expression ofβ-catenin was detected on the cell membrane in normal colorectal mucosa and adenoma, whereas in adenocarcinoma it was found in cytoplasmic and/or nuclear region(P<0.05). Moreover, the rate of abnormalβ-catenin expression was higher in adenocarcinoma compared to both normal colorectal mucosa and adenoma(P<0.05). Expression of MT1-MMP in normal colorectal mucosa and adenoma was negative, while the expression in adenocarcinoma was positive,(P<0.05). The expressions of PARG, PARP, NF-κB,β-catenin and MT1-MMP in adenocarcinoma showed a positive association with the depth of invasion, lymphatic metastasis and Duke’s stage (all P<0.05);Nevertheless, the above expression had no correlation at all with sex, age, site, size or differentiation (all P>0.05). PARG expression shows a positive correlation with the expressions ofβ-catenin , MT1-MMPand NF-κB ((r=0.274, 0.216, 0.332, P<0.05) respectively, while PARP expression shows a positive correlation with the expressions ofβ-catenin , MT1-MMP and NF-κB(r=0.291,0.027, 0.398,P<0.05) respectively。
2.The expressions of PARP, NF-κB,β-catenin and MT1-MMP detected by western blot in 5-AIQ-treated lovo cells were weaker than those in 5-AIQ-untreated lovo cells(P<0.05),however PARG expression wasn’t changed obviously(P>0.05). By immunofluorescence method, the expression ofβ-catenin was in cytolymph and/or in nucleus.
3.The expressions of PARG, PARP, NF-κB,β-catenin and MT1-MMP detected by western blot in GLTN-treated lovo cells were weaker than those in GLTN-untreated lovo cells(P<0.05).
CONCLUSION: The expression of PARG related to the expression of PARP, NF-κB,β-catenin and MT1-MMP in colorectal carcinoma. The expression of PARG, PARP, NF-κB,β-catenin and MT1-MMP were probably related to the development of colorectal carcinoma. PARG maybe playing an important roles in the regulation of NF- B,β-catenin and MT1-MMP expressions in colorectal carcinoma through regulation of PARP.
引文
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