Please use this identifier to cite or link to this item: http://scholarbank.nus.edu.sg/handle/10635/14077
Title: Molecular analysis of the p14 ARF-hdm2-p53 regulatory pathway in breast carcinoma
Authors: HO GAY HUI
Keywords: p53, hdm2, p14ARF, E2F-1, E2F-4, breast carcinoma
Issue Date: 1-Jun-2004
Source: HO GAY HUI (2004-06-01). Molecular analysis of the p14 ARF-hdm2-p53 regulatory pathway in breast carcinoma. ScholarBank@NUS Repository.
Abstract: Breast cancer is the most common female cancer worldwide. The main objective of this study was to verify the hypothesis that the p14ARF-hdm2-p53 regulatory pathway and E2F transcription factors play important roles in breast carcinogenesis. This study was conducted in four phases. The initial project investigated p53 mutations, p14ARF mutations and mRNA expression and hdm2 gene amplification. The genetic alterations were identified in 25% of primary breast cancers and 64% of human breast cell lines with p53 mutations being the predominant aberration. The second phase evaluated p53 expression by immunohistochemistry in invasive breast cancers and detected nuclear reactivity in 35% of the 105 Asian women. p53 immunopositivity correlated with poorer overall survival. The third project examined paired samples of DCIS and normal breast tissue samples and revealed p53 mutations in 20% of the DCIS lesions, but, none of the corresponding normal breast tissues. These findings support the hypothesis that p53 mutations are important in the development of DCIS. Mutational and expression analyses of E2F-1 and E2F-4 were performed in primary breast cancers and matched samples of metastatic lymph nodal tissues and normal breast tissues. Reduced expression level of both transcription factors was observed in 70% of the 10 primary tumours and in all the metastatic lymph nodal tissues. This marked downregulation of the E2Fs in tumour tissues suggests a likely tumour suppressive role in breast carcinogenesis and that they may be important in the development of metastasis.
URI: http://scholarbank.nus.edu.sg/handle/10635/14077
Appears in Collections:Ph.D Theses (Open)

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