Reduced expression of MAD2 protein in association with defective mitotic checkpoint in breast cancer cells

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Reduced expression of MAD2 protein in association with defective mitotic checkpoint in breast cancer cells

 

Author: Ling, Chi-kin Peter
Title: Reduced expression of MAD2 protein in association with defective mitotic checkpoint in breast cancer cells
Year: 2004
Subject: Hong Kong Polytechnic University -- Dissertations
Carcinogenesis
Breast -- Cancer -- Cytodiagnosis
Cell cycle
Department: School of Nursing
Pages: x, 64 leaves : ill. (some col.) ; 30 cm
Language: English
InnoPac Record: http://library.polyu.edu.hk/record=b1781168
URI: http://theses.lib.polyu.edu.hk/handle/200/1625
Abstract: Mitotic checkpoint plays a significant role in accurate chromosome segregation in mitotic cells. Loss of function of this mitotic checkpoint will contribute to tumorigenesis in human cells. MAD2 (mitotic-arrest deficient 2) protein is the key factor controlling the mitotic checkpoint. The present study aimed to find out the significance of MAD2 protein expression to mitotic checkpoint control in breast cancer cells. Mitotic index measurement and cell cycle analysis were used to investigate the competence of the mitotic checkpoint in human breast cancer cell lines, and we found that the mitotic checkpoint was defective in one (T-47D) out of three (33%) of the tested breast cancer cell lines (MCF-7, MDA-MB-231 and T-47D). The MAD2 protein in breast cancer cell lines as demonstrated by Western blotting also showed that the reduced MAD2 protein expression was associated with defective mitotic checkpoint. Further study in human breast tissues by immunohistochemistry was performed to correlate the change of MAD2 protein expression in the progression of human breast carcinoma and to find out if MAD2 expression has any clinical significance. The cases showing positive expression of MAD2 protein in invasive ductal carcinoma (17.5%) and ductal carcinoma in situ (24.1%) were significantly decreased (P=0.005) as compared to those in the benign breast lesions (53.6%). However, expression of MAD2 protein was not associated (P>0.05) with tumor size, lymph node status, nuclear grade or other clinicopathologic factors. Collectively, these findings suggest that defective mitotic checkpoint characterized by the reduced expression of MAD2 may contribute to tumor progression in breast carcinogenesis.

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