Use this URL to cite or link to this record in EThOS: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.294211
Title: A study of the regulation of polyamine acetylation in human breast cancer cells
Author: Quick, Deborah M.
Awarding Body: University of Aberdeen
Current Institution: University of Aberdeen
Date of Award: 1994
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Abstract:
The presence of elevated acetylpolyamines in breast cancer tissue suggests that polyamine catabolism may be aberrant in neoplastic development. For these reasons we chose to study the regulation of SAT, the rate limiting enzyme of polyamine catabolism in the human breast cancer cell line (T47-D). T47-D cells grew in DMEM supplemented with foetal calf serum and insulin. Spermine was the predominant intracellular polyamine > spermidine >> putrescine; no acetylpolyamines were detected. Polyamine accumulation in the cultured cells reached a peak at 72h concomitant with maximal DNA synthesis. SAT activity increased during the culture period with N8-SAT being the predominant isoform detected in untreated T47-D cells. Growth inhibitory concentrations of the polyamine analogue, methylglyoxal bis(guanylhydrazone) (MGBG) produced significant induction of N1-SAT activity in addition to depleting the intracellular polyamines. Pre-treatment of T47-D cells with DFMO enhanced the induction of SAT by low concentrations of MGBG whilst the induction was attenuated when higher concentrations of MGBG were used. The calcium ionophore, tetronasin produced a dose-dependent induction of N1-SAT activity. Despite the growth inhibition by the ionophore there was no significant effect on the total polyamine content. In addition tetronasin potentiated the induction of N1-SAT activity by both MGBG and sodium butyrate. Tetronasin enhanced the accumulation of MGBG by the T47-D cells. Addition of calcium ions directly to the SAT assay stimulated MGBG-induced SAT activity, whilst basal, untreated SAT activity was unaffected. Chelation of extracellular calcium prevented the induction of N1-SAT by tetronasin, whilst the SAT activity induced by the combination of MGBG and tetronasin was only minimally affected.
Supervisor: Not available Sponsor: Not available
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral
EThOS ID: uk.bl.ethos.294211  DOI: Not available
Keywords: Biochemistry Biochemistry Medicine
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