TITLE

PRELIMINARY ASSESSMENT OF P53 AND RELATED GENES AS THERAPIES FOR OESOPHAGEAL CANCER

AUTHOR(S)
Abouda, G.F.; Pohler, E.; Dillon, J.F.
PUB. DATE
April 2003
SOURCE
Gut;Apr2003 Supplement 1, Vol. 52, pA57
SOURCE TYPE
Academic Journal
DOC. TYPE
Article
ABSTRACT
Background: Oesophageal cancer is a disease with a dreadful prognosis and a rapidly rising incidence. New therapies For treatment of this cancer need to be evaluated and in this area gene therapy may have a role to play. Aims: Using liposomes as a transfer agent, to assess the expression of the p53 gene (human and mouse wild type and mutants) in oesophageal cancer cell lines, estimating the degree of apoptosis in these cell lines. In addition, to determine the effect the mouse Scottin gene, a p53 inducible pro-apoptotic gene, on cell survival. Method: Two squamous cell carcinoma cell lines (OE21 and KYSE30), and two adenocarcinoma cell lines (OE33 and OE19) were transfected with human and mouse wild type p53 constructs. Following 48 hours incubation, cells were analysed by Western blotting (to examine expression of p53) and FACScan (to detect apoptosis). Cells were also transfected with mutant forms of both the human and mouse p53 genes, and the effects of these on the cell survival compared to the wild types. Finally, cells were transfected with the mouse Scottin gene and the consequences of its expression determined. Results: p53 expression was found to be higher in OE33 and OE21 cells by Western blotting than in KYSE30 and OE19. FACScan analysis revealed high levels of apoptosis were achieved in OE21 and OE 33 cells following wild type p53 expression. Apoptosis was also observed in KYSE30 cells but to a lesser degree. In all three of these cell lines, this effect was more pronounced using the mouse p53 gene compared to the human p53. The levels of apoptosis observed were increased further in OE21, OF33 and KYSF30 cells following expression of the mutant forms of both human and mouse p53. However, highest degrees of apoptosis were obtained in these cell lines with expression of the Scottin gene. No apoptosis was seen following expression of any of the constructs in OE19 cells. Conclusion: We have succeeded in inducing apoptosis in three different oesophageal...
ACCESSION #
9747672

 

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