Expression profiles of MAD2L1, p53 and Rb proteins with MAD2L1 promoter methylation status in Chinese breast cancer patients

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Expression profiles of MAD2L1, p53 and Rb proteins with MAD2L1 promoter methylation status in Chinese breast cancer patients


Author: Chong, Wai-ki
Title: Expression profiles of MAD2L1, p53 and Rb proteins with MAD2L1 promoter methylation status in Chinese breast cancer patients
Degree: M.Sc.
Year: 2006
Subject: Hong Kong Polytechnic University -- Dissertations.
Breast -- Cancer -- Patients -- China -- Hong Kong.
Breast -- Cancer -- Epidemiology.
Department: Dept. of Health Technology and Informatics
Pages: xiv, 102 leaves : ill. (some col.) ; 30 cm.
Language: English
InnoPac Record:
Abstract: Breast cancer is the most frequently diagnosed cancer in women. The mechanisms of its carcinogenesis remain incompletely understood. Breast cancer is heterogeneous. Most of them display some degree of aneuploidy, which can be prevented in some extent by normal regulation of a mitotic spindle checkpoint. Disruption of Mitotic arrest deficient 2 human homolog like 1 (MAD2L1) expression causes defect in spindle checkpoint. Increasing evidences indicate that aberrant methylation of specific gene promoter region results in transcriptional silencing. The project is focused on the study of the molecular genetics, pathobiological and clinical characteristics in 40 cases of breast cancer. The study consists of two areas. The first is aimed at investigation of MAD2L1, Retinoblastoma (Rb) and p53 protein expressions between cancerous and normal breast by immunohistochemical analysis. MAD2L1 is a key factor of the mitotic spindle checkpoint. Rb is in the regulation of cell cycle progression whereas p53 is a transcription factor that regulates the cell cycle to suppress cancer. Result of immunohistochemical study showed that 80% tumor had positive MAD2L1 expression. Positive associations between MAD2L1 expression with tumor grade, tumor size, p53 and human epidermal receptor-2 (HER-2/neu) status were found. 92.5% tumor showed positive Rb but no prognostic value was identified. 32.5% tumor showed positive p53 expression, which showed correlation with higher tumor grade and negative progesterone receptor (PR) expression. Besides, there was a trend of correlation between high p53 expression and negative estrogen receptor (ER) expression. As increased MAD2L1 protein expression was found to have significant correlation with tumor grading, it might be added to the routine panel of markers for examination of breast cancer. The second area is the study of methylation status of MAD2L1 promoter region in carcinogenesis of breast cancer by methylation-specific polymerase chain reaction (MSP). The promoter methylation may be responsible for changes in checkpoint protein levels inducing mitotic checkpoint dysfunction and chromosomal instability. In MSP analysis, 45% and 83 % of tumor cases showed methylation of 5'CpG islands within MAD2L1 gene promoter by using 2 sets of designated primer. No correlation was seen between MAD2L1 protein expression and its methylation status of promoter region. Nevertheless, a trend of correlation between methylation of MAD2L1 promoter region and tumor size was found.

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