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The Expression Of Plexin-B2 In Tumor And The Molecular Mechanism Of Plexin-B2 Promoting Carcinoma Invasion And Metastasis

Posted on:2012-04-07Degree:MasterType:Thesis
Country:ChinaCandidate:L L YangFull Text:PDF
GTID:2214330362457429Subject:Gynecological oncology
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Objective: To explore the expression of plexin-B2 in human cervical cancer tissues and in cervical cancer cells. In addition, the mechanism of plexin-B2 on cervical cancer cell invasion, metastasis and proliferation was investigated in vitro.Methods: Plexin-B2 expression was analyzed in normal and cervical cancer tissues by immunohistochemical staining, as well as in three human cervical cancer cell lines (Hela,Siha,C33A) by RT-PCR and western blot analyses. Furthermore, endogenous plexin-B2 expression was suppressed by plexin-B2 siRNA in Siha cells, which some little overexpress plexin-B2 than others. Protein levels of Plexin-B2, AKT and P-AKTSer473 were examined by western blot analysis. Cell migration, invasion and proliferation were measured with wound healing, boyden chamber and CCK-8 assays, respectively, and the cytoskeleton was monitored via F-actin staining.Results: There was no significant difference between the expression of Plexin-B2 in normal cervical tissues and cervical cancer tissues.Plexin-B2 expression was positively correlated with FIGO stage and lymphatic metastasis. The more advanced FIGO stage and positive lymphatic metastasis, the higher expression rate of Plexin-B2. Siha cells displayed the some little higher plexin-B2 expression at both the mRNA and protein levels among the three tested human cervical cancer cell lines.Silencing of plexin-B2 in Siha cells significantly suppressed the expression of P-AKTser473 in Siha cells, but it did not alter total AKT expression. In addition, silencing of plexin-B2 in Siha cells inhibited cell migration, invasion, proliferation and reorganization of the cytoskeleton.Conclusion The aberrant expression of plexin-B2 may be associated with the malignant progression of cervical cancer. Moreover, Plexin-B2 may contribute to migration, invasion and proliferation of cervical cancer cells, probably via phosphorylation of AKT at Ser473, suggesting that plexin-B2 might be a useful biomarker and/or a novel therapeutic target. Object: To explore the expression and significance of Plexin-B2 in human breast cancer, and whether its co-expression with human epidermal growth factor receptor 2 (Her-2) has correlation with tumor aggressiveness. Methods: The protein expression of Plexin-B2 and Her-2 were investigated by immunohistochemistry SP method in 112 cases of breast carcinoma. The protein expression of Plexin-B2 was detected in 15 cases of normal breast tissues as well. Results: There was no significant difference between the expression of Plexin-B2 in the breast cancer carcinoma cells and in the epithelia cells of normal breast tissues'mammary lobules and ducts (P> 0.05), the expression rates of them were 69.64% and 60.00% respectively. Plexin-B2 was detected positive expression in 44.62% peri-cancerous microvessels of breast cancer tissues,whereas, no positivity was observed in microvessels of normal breast tissues. There was positive relationship about Plexin-B2 expression between tumor cells and pericancerous microvessels in human breast cancer (r=0.593,P = 0.000), which were correlated with clinical stage and lymph node metastases( P < 0. 05). Plexin-B2 expression of tumor cells was also found to be associated with histological grade ( P < 0. 05). Tumors co-expressing Plexin-B2 and Her-2 were characterized by worse staging and higher incidence of lymph node metastases than those expressing Plexin-B2 alone, the difference was significant ( P < 0. 05).Conclusion: The aberrant expression of plexin-B2 may be associated with the malignant progression of breast cancer. Moreover, Plexin-B2 may contribute to invasive and metastatic behavior of tumors when co-expressed with Her-2.
Keywords/Search Tags:Plexin-B2, cervical cancer, invasion, metastasis, Her-2, Breast neoplasm
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