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Title: Molecular analysis of the homeobox gene BarX2, a candidate tumour-suppressor gene in ovarian cancer
Author: Li, Li
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2001
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The objective of this study is to investigate the role of BarX2 gene as a candidate tumour-suppressor gene in human epithelial ovarian cancer. Active work on this project was commenced by the candidate on 4th January 1998. The scope of the project thus far has involved the following: 1) using PCR based polymorphic microsatellites to further refine the region of frequent loss of heterozygosity on chromosome 11q24 in DNA blood/tumour pairs from patients with ovarian cancer and colorectal cancer which confirms that BarX2 region is subject to LOH in clinical cancers; 2) using RT - PCR and Northern blot to detect the expression pattern of Barx2 in cancer cell lines and cancer tissues; 3) Mutation analysis using SSCP, DHPLC and Fluorescence DNA sequencing to define the molecular basis of BarX2 gene in cancer cell lines and blood/tumour pairs from patients with ovarian and colorectal cancer; 4) performing functional studies of BarX2 by using an expression vector for this genein ovarian cancer cell lines; 5) using drug- sensitivity testing in vitro to detect whether introduction of Barx5 gene into a platinum resistant ovarian cancer cell line affects the sensitivity of this cell line to Cis-platinum. Preliminary results showed that: 1) Barx2 gene has downregulated expression in at least some ovarian cancer cells and is associated with disease progression in ovarian cancer as well; 2) Altered transcript size is seen in some ovarian cancer cell; 3) The Barx2 gene can suppress the growth of ovarian cancer cell lines and tumour cell invasion in matrigel; 3) Introduction of Barx2 into a platinum resistant ovarian cancer cell line increases the sensitivity of this cell line to Cisplatinum. These results suggest that Barx2 gene may play a important role as tumour suppressor gene in carcinogenesis. Further work will focus on mutation analysis and methylation studies in cell lines and clinical samples in order to define the physical molecular basis of BarX2 abnormalities; and dissection of the matrigel invasion phenotype using cell migration and cell adhesion assays for BarX2 transfected cells.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (M.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available