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Title: The putative oncogene EEF1A2 and its role in breast and ovarian cancer
Author: Tomlinson, V.
Awarding Body: University of Edinburgh
Current Institution: University of Edinburgh
Date of Award: 2007
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I investigated the expression of eEF1A2 in breast and ovarian cancers at both the RNA and protein levels. I identified eEF1A2 overexpression in up to two-thirds of breast cancers and moderate to high levels of eEF1A2 expression were associated with estrogen receptor positive cancers (p=0.0087). In ovarian cancers eEF1A2 was found to be expressed in up to one-third of cancers and was highly expressed in clear cell carcinomas. The majority of ovarian cancers analysed showed amplification of the EEF1A2 locus regardless of whether they expressed eEF1A2, suggesting this is not the only mechanism mediating the overexpression of the elongation factor. Mutation analysis of the exonic sequence of EEF1A2 in low copy number ovarian cancers led to the identification of only one sequence variant that would not be predicted to alter the sequence of the protein but may have an effect on post transcriptional regulation of gene expression. Immunofluorescence analysis of the sub cellular localisation of eEF1A1 and eEF1A2 in breast (MCF-7) and ovarian (PEO1) cancer cell lines suggests that the two isoforms show a similar diffuse cytoplasmic localisation with some concentration in the perinuclear region of the cell. eEF1A1 and eEF1A2 partially co-localise with tubulin in the perinuclear region and with F-actin in cellular protrusions. Finally, analysis of eEF1A2 function in the breast cancer cell line MCF-7 using RNA interference of EEF1A2 showed that partial ablation of eEF1A2 does not alter the rate of proliferation, cell cycle distribution or the percentage of cells in apoptosis. Therefore, eEF1A2 is frequently overexpressed in breast and ovarian cancers and this overexpression does not appear to be consistently mediated by gene amplification, mutation or methylation.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID:  DOI: Not available