The Relationship Between N-myc Copy Number or Expression and Resistance to Therapy in Human Neuroblastoma Cell Lines

Livingstone, Anne (1993) The Relationship Between N-myc Copy Number or Expression and Resistance to Therapy in Human Neuroblastoma Cell Lines. MSc(R) thesis, University of Glasgow.

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Abstract

The copy number of the N-myc oncogene provides a prognostic index for neuroblastoma. The mechanism for this is not known, but may be related to cellular resistance to radiation or cytotoxic drugs. Seven human neuroblastoma cell lines were used to investigate the relationship between N-myc copy number or expression and sensitivity to ionising radiation and cisplatin. N-myc copy number was assessed by Southern blotting and hybridisation using the p-Nbl probe. The signal produced from DNA of the cell lines was compared with that of human placental DNA which has single copy N-myc (the normal copy number for diploid cells), A range of N-myc copy numbers from 1 - 800 was found. Expression levels of N-myc messenger RNA were compared by "dot-blotting" and subsequent hybridising to the p-Nbl probe. Radiosensitivity was investigated by irradiating multicellular tumour spheroids or cell monolayers using a 60Co source, (dose range 0.5 - 5 Gy). Survival curves were produced using both colony formation and spheroid regrowth delay as end points. The response to radiation was assessed by surviving fraction at 2 Gy (SF2); values ranged from 0.13 - 0.52. Sensitivity to cisplatin was indicated by comparison of isoeffective concentrations (concentration required to produce 1 log cell kill) from survival curves produced as above. These concentrations ranged from 7.5 - 13 muM. Cisplatin studies showed a border-line correlation between N-myc copy number (though not expression) and resistance to this drug. If this relationship is causal it may explain why treatment fails in those patients with elevated N-myc copy number. However, no correlation was found between N-myc copy number or expression and sensitivity to radiation. It is possible that N-myc amplification confers resistance to some, but not all, treatments used in the therapy of neuroblastoma. Further investigations along these lines may lead to the identification of agents which are most appropriate for the treatment of neuroblastoma with amplified N-myc gene.

Item Type: Thesis (MSc(R))
Qualification Level: Masters
Additional Information: Adviser: R J Mairs
Keywords: Medicine, Cellular biology, Oncology
Date of Award: 1993
Depositing User: Enlighten Team
Unique ID: glathesis:1993-74621
Copyright: Copyright of this thesis is held by the author.
Date Deposited: 13 Nov 2019 15:58
Last Modified: 13 Nov 2019 15:58
URI: https://theses.gla.ac.uk/id/eprint/74621

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