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dc.contributor.advisor Wada, Randal K en_US Tuthill, Matthew Charles en_US 2008-03-30T07:22:42Z 2008-03-30T07:22:42Z 2003-12 en_US
dc.identifier.citation Tuthill, Matthew Charles (2003) N-myc oncogene expression in neuroblastoma is dependent on Sp1 and Sp3. Ph.D. dissertation, University of Hawai'i, United States -- Hawaii. en_US
dc.description.abstract Regulation of N-myc oncogene expression is an important determinant of the biological behavior of neuroblastoma. The N-myc promoter contains several potential binding sites for transcription factors of the Sp1 family. Mutation of a CT-box motif contained within a 26 base pair region required for N-myc downregulation by retinoic acid decreased basal transcriptional activity and altered DNA-protein interactions of the promoter, while mutations flanking this motif did neither. On gel shift this region generated 3 specific DNA-protein complexes that were reliant on wild type sequence of the core CT element within it. Both Spl and Sp3 bound to the wild type probe as distinct complexes in specifically retarded bands, while neither protein was present on mutated sequences. Lysates from Drosophila S2 cells expressing exogenous Sp1 and Sp3 proteins were able to reproduce the gel shift complexes seen with neuroblastoma nuclear extract. Transient transfections of S2 cells showed that individually or together, Sp1 and Sp3 were able to trans-activate a N-myc CT-box-containing luciferase reporter construct in a dose-dependent manner. Conversely, transfection of CT-box oligonucleotide was able to decrease endogenous N-myc expression in neuroblastoma cells. Together these results suggest that the CT-box element serves a critical functional role, and in the basal state allows for N-myc transactivation by Spl and Sp3. en_US
dc.language.iso en-US en_US
dc.publisher University of Hawaii at Manoa en_US
dc.relation Theses for the degree of Doctor of Philosophy (University of Hawaii at Manoa). Biomedical Sciences (Cell & Molecular Biology); no. 4319 en_US
dc.rights All UHM dissertations and theses are protected by copyright. They may be viewed from this source for any purpose, but reproduction or distribution in any format is prohibited without written permission from the copyright owner. en_US
dc.rights.uri en_US
dc.subject N-myc en_US
dc.subject Neuroblastoma en_US
dc.subject Sp1 en_US
dc.subject Sp3 en_US
dc.subject Molecular biology en_US
dc.subject Cellular biology en_US
dc.title N-myc oncogene expression in neuroblastoma is dependent on Sp1 and Sp3 en_US
dc.type Thesis en_US
dc.type.dcmi Text en_US
dc.contributor.department Biomedical Sciences (Cellular & Molecular Biology) en_US 2003-05 en_US
local.identifier.callnumber AC1 .H3 no. 4319 en_US
local.thesis.degreelevel PhD en_US

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