Relationship Of Poly(adp-ribose) Glycohydrolase(parg) With �'-CATENIN And Membrane Type 1 Matrix Metallopro-teinase(mt1-mmp) In Colorectal Carcinoma

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.