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Introduction：Breast cancer is the most common malignancy in women, its pathogenesisrelated to many tumor suppressor genes, including "ww domain contamingoxidoreductase", WWOX gene. As a new tumor suppressor gene found inrecent years, the study of WWOX has been carried out widely in a variety oftumors. The function of VEGF, MMP-2, p53, caspase-3and PCNA protein inthe development of breast cancer has been very clear, which were studieddeeply. In order to investigate the function of WWOX protein deletion in thedevelopment of breast cancer and the possible mechanisms of WWOX proteinplaying its role, we examined the protein expression of WWOX in sporadicbreast cancer and breast fibroadenoma tissue, as well as VEGF, MMP-2, p53,Caspase-3and PCNA in sporadic breast cancer tissue, and analyzed therelationship between the WWOX protein expression level withclinicopathological features and five kinds of protein expression levels.Materials and methods：1、Tissue specimens190cases pathologic specimens of sporadic breast cancer were collectedfrom nocology wards of the first hospital affiliated of Jilin Universitybetween January2009to June2011, which clinical stage was made accordingto TNM staging made by the International Union of Against Cancer in1997;52cases of breast fibroadenoma were collected meanwhile. These patients werefemale, aged21to72years, without chemotherapy, radiotherapy and otheranticancer treatment before the operation.2、Reagent Rabbit anti-human WWOX polyclonal antibody was purchased fromBritish Abcam companies (ab33248), rabbit anti-human antibody of VEGF(sc-80437), MMP-2(sc-71595), p53(sc-53394), Caspase-3(sc-56046) andPCNA (sc-53407) were purchased from Santa Cruz; Normal goat serumblocking solution was purchased from Wuhan Boster; SP hypersensitivityconcentration (rabbit) kit (KIT-0100R), was purchased from Fuzhou Maixinbiological technology development Limited company; DAB chromogenic kitwas purchased from Beijing Zhongshan Golden Bridge Biotechnology Limitedcompany.3、MethodsBy immunohistochemical assay, we detected WWOX protein expressionlevels of190cases of sporadic breast cancer and52cases of breastfibroadenoma specimens, VEGF, MMP-2, p53, caspase-3and PCNA proteinexpression levels of the190cases of sporadic breast cancer. And therelationship between the WWOX protein expression level withclinicopathological features and five kinds of protein expression levels wasanalyzed.SPSS16.0statistical package was used for data analyzing on theexperimental results, the Pearson chi-square test for the correlation betweeneach parameter, setting P<0.05statistically significant.Results：In Breast cancer tissues, WWOX protein positive expression rate was46.3%, in breast fibroadenoma tissue, that was82.7%; Compared withfibroadenoma, the positive rate of WWOX protein expression was significantlydecreased in breast cancer tissue, the difference was statistically significant(P<0.001); The positive expression rate of VEGF, MMP-2, p53, caspase-3andPCNA in breast cancer tissues were70.0%,65.3%,61.1%,37.9%and85.3%;Among patients of age≤50years or premenopausal patients, WWOX proteinexpression level was significantly higher(P<0.001); Among patients with lymph node metastasis, WWOX protein expression level was significantlylower (P=0.014); In VEGF negative tissues, WWOX protein expression levelwas significantly higher than VEGF positive tissues(P=0.016); WWOX proteinexpression level of Caspase-3positive tissues was significantly higher thanCaspase-3-negative group (P=0.046); Compared with the rest of parameters,there was no significant differences.Conclusion：1. Compared with breast fibroadenoma, WWOX protein expression levelin sporadic breast cancer was significantly reduced;2. The deletion of WWOX protein expression is more significantly in theelder, postmenopausal groups of sporadic breast cancer, and it may contributedto lymph node metastasis;3. WWOX playing a tumor suppressor role may be generated due to thedown regulation of VEGF, up regulation of caspase-3.
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