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Analysis of NEIL3 expression : a possible resistance factor to cancer chemotherapy in paediatric cancer cells

Duweb, AAI 2015, Analysis of NEIL3 expression : a possible resistance factor to cancer chemotherapy in paediatric cancer cells , MRes thesis, Enviroment and Life Science.

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Abstract

NEIL3 is the largest of three homologs of the bacterial Nei protein in mammalian cells. It has been shown to have DNA glycosylase activity in vitro, excising oxidised purine and pyrimidine bases from both single- and double-stranded DNA. Additionally, NEIL3 has recently been shown to release oxidised bases from telomeric regions of DNA. While NEIL3 shows a restricted expression pattern in normal human cells, previous studies have shown that NEIL3 is highly expressed in various cancer cell lines when compared with normal counterparts. Furthermore, high expression levels of NEIL3 were associated with development of metastases in patients with primary malignant melanoma. However, no one has looked at the expression of NEIL3 in paediatric cancer cells, or attempted to correlate the expression of NEIL3 with proteins involved in telomere length maintenance. Therefore, the aim of this project was to determine the gene expression levels of NEIL3 in paediatric cancer cell lines and to determine any association between the levels of NEIL3 expression and the presence or absence of telomerase in these cells. Gene expression of NEIL3, hTERT and POT1 was measured by qRT-PCR in two cell lines of acute lymphoblastic leukaemia (ALL; steroid sensitive and steroid resistant cells), osteosarcoma, hepatoblastoma and medulloblastoma tumours. An initial assessment of whether the levels of NEIL3 expression are indicative of the response of paediatric tumours to sensitivity to DNA damaging agents was also carried out using the hepatoblastoma and the ALL cells. The results confirmed that NEIL3 was highly expressed in all cell lines tested and that the relative levels of NEIL3 and telomerase mRNA was significantly higher in steroid resistant ALL cells than in the steroid sensitive ALL cells. However, there was no correlation between the expression of NEIL3 and the presence or absence of telomerase. ALL and hepatoblastoma cells were sensitive to cisplatin, doxorubicin and tert-butyl hydroperoxide (t-BHP), as a decrease in cell growth was observed at each concentration of the compounds tested. Results also indicate that following treatment with t-BHP, growth of the steroid sensitive ALL cells was significantly more inhibited than that of the resistant ALL cell line. Therefore, NEIL3 could be a resistance factor to cancer chemotherapy in paediatric cancer cells and may be a novel target for the treatment of paediatric cancers.

Item Type: Thesis (MRes)
Schools: Schools > School of Environment and Life Sciences > Biomedical Research Centre
Funders: Scholarship
Depositing User: AAI Duweb
Date Deposited: 22 Feb 2016 13:46
Last Modified: 22 Feb 2016 13:46
URI: http://usir.salford.ac.uk/id/eprint/37305

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