Please use this identifier to cite or link to this item: http://hdl.handle.net/10125/1258

Files

File Description SizeFormat 
uhm_phd_4392_r.pdfRestricted for viewing only15.71 MBAdobe PDFView/Open
uhm_phd_4392_uh.pdfFor UH users only15.71 MBAdobe PDFView/Open

Item Summary

Title: The LOX and LOXL2 amine oxidases in colon and esophageal cancer
Authors: Fong, Sheri Fumiko Tsuda
metadata.dc.contributor.advisor: Csiszar, Katalin
Keywords: LOX
Amine oxidases
Esophageal cancer
Colon cancer
Lysyl oxidase
Molecular biology
Genetics
Oncology
Issue Date: Dec-2003
Publisher: University of Hawaii at Manoa
Citation: Fong, 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.
Abstract: Several 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.
URI: http://hdl.handle.net/10125/1258
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.
Appears in Collections:Ph.D. - Biomedical Sciences (Cell & Molecular Biology)



Items in ScholarSpace are protected by copyright, with all rights reserved, unless otherwise indicated.