The LOX and LOXL2 amine oxidases in colon and esophageal cancer

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dc.contributor.advisorCsiszar, Katalin
dc.contributor.authorFong, Sheri Fumiko Tsuda
dc.contributor.departmentBiomedical Sciences (Cellular & Molecular Biology)
dc.date.accessioned2008-04-17T18:34:51Z
dc.date.available2008-04-17T18:34:51Z
dc.date.graduated2003-12
dc.date.issued2003-12
dc.description.abstractSeveral members of the lysyl oxidase family of copper-dependent amine oxidases have been implicated in tumor development. The Iysyl oxidase (LOX) and LOX-like 2 (LOXL2) genes have been mapped to chromosomal regions affected by loss of heterozygosity (LOH) in several cancers, including those of the colon and esophagus. Indeed, there have been numerous reports of reduced LOX and a few reports of reduced LOXL2 expression in various cancers. Identification of microsatellite markers within the LOX locus and the LOXL2 gene allowed for evaluation ofthe status of these gene alleles in colon and esophageal tumors. There was significant LOH of the LOX locus in colon tumors that was accompanied by reduced mRNA expression and a spectrum of alterations and mutations affecting the LOX gene. This study demonstrated, for the first time, that genetic events, namely LOH, deletions and mutations ofthe LOX gene, were responsible, at least partly, for the reduction of LOX gene expression. There was also significant LOH of the LOXL2 gene in both colon and esophageal tumors. However, instead of a reduction of LOXL2 expression, there was increased expression that correlated with less differentiated tumors and absent elastosis, both indicators of poor prognosis. Further studies indicated that both LOX and LOXL2 are absent in non-invasive tumor cell lines but re-expressed in invasive cell lines, likely as part of the thelial-mesenchymal transition that occurs in the last steps of tumorigenesis to facilitate metastasis. The results presented and research strategy outlined in this dissertation will define the importance of LOXL2 amine oxidase activity and protein interactions in the critical but poorly understood process oftumor cell migration and invasion.
dc.identifier.citationFong, Sheri F. T. (2003) The LOX and LOXL2 amine oxidases in colon and esophageal cancer. Ph.D. dissertation, University of Hawai'i, United States -- Hawaii.
dc.identifier.urihttp://hdl.handle.net/10125/1258
dc.language.isoen-US
dc.publisherUniversity of Hawaii at Manoa
dc.relationTheses for the degree of Doctor of Philosophy (University of Hawaii at Manoa). Biomedical Sciences (Cell & Molecular Biology); no. 4392
dc.rightsAll 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.
dc.rights.urihttps://scholarspace.manoa.hawaii.edu/handle/10125/865
dc.subjectLOX
dc.subjectAmine oxidases
dc.subjectEsophageal cancer
dc.subjectColon cancer
dc.subjectLysyl oxidase
dc.subjectMolecular biology
dc.subjectGenetics
dc.subjectOncology
dc.titleThe LOX and LOXL2 amine oxidases in colon and esophageal cancer
dc.typeThesis
dc.type.dcmiText
local.identifier.callnumberAC1 .H3 no. 4392
local.thesis.degreelevelPhD

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