| Summary: | 碩士 === 義守大學 === 生物醫學工程學系碩士班 === 99 === Breast cancer, a malignant tumor which severely harms women’s health, has jumped to the first place in the incidence of women-specific malignancies in Taiwan. Therefore, it is a critical issue to explore the underlying mechanisms as well as the therapeutic targets for breast cancer.
DNA mutation is a common phenomenon in tumorigenesis. The MRN protein complex, consisting of MRE11, RAD50 and NBS1, is involved in both DNA damage repair pathway and cell cycle checkpoint control. In clinical studies, MRN complex abnormalities are frequently observed in tumor, with the underlying mechanism still poorly understood. Therefore, it is an interesting issue to investigate the possible involvement of NBS1 and RAD50 proteins in human breast cancer. We analyzed the expression of NBS1 and RAD50 proteins in breast cancer tissues by immunohistochemistry, and correlated with the clinical pathological characteristics. We found the significant positive correlation between NBS1 expression and clinical stage group (p = 0.006), age at diagnosis (p = 0.005), and lymph node (LN) metastasis (p = 0.001). The high NBS1 expression was an independent marker of poor prognosis in breast cancer. On the other hand, using the shRNA/lentivirus technique, we observed that down-regulation of NBS1 protein expression in MDA-MB231 breast cancer cell line, led to retarded cell proliferation. The result suggested NBS1 play an important role in breast cancer development. Contrary to NBS1 protein, we found a significant negative correlation between RAD50 expression and clinical staging (p < 0.0001), tumor size (p = 0.045), and lymph node (LN) metastasis (p = 0.034). The high RAD50 expression was associated with good prognosis in breast cancer. Hopefully, this study will lead to a better understanding of the role of the two proteins in breast cancer development.
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