Lysyl oxidase-like 2 expression is increased in colon and esophageal tumors and associated with less differentiated colon tumors.
Lysyl oxidase-like 2 (LOXL2) belongs to an amine oxidase family whose members have been implicated in crosslink formation in stromal collagens and elastin, cell motility, and tumor development and progression. We previously demonstrated the association between increased LOXL2 expression and invasive/metastatic behavior in human breast cancer cells and mouse squamous and spindle cell carcinomas, interaction between LOXL2 and SNAIL in epithelial-mesenchymal transition, and localization of the LOXL2 gene to 8p21.2-21.3, within a minimally deleted region in several cancers, including colon and esophagus. In the present study, we analyzed LOXL2 expression in colon and esophageal tumors, and explored methylation as a regulator of LOXL2 expression. Immunohistochemistry using normal tissues demonstrated intracellular localization of LOXL2 in colonic enteroendocrine cells and esophageal squamous cells at the luminal surface, but not in mitotically active cells. Tissue array analysis of 52 colon adenocarcinomas and 50 esophageal squamous cell carcinomas revealed presence of LOXL2 expression in 83 and 92% of the samples, respectively, and a significant association between increased number of LOXL2-expressing cells and less-differentiated colon carcinomas. We determined that the methylation status of the 1150 bp 5' CpG island may contribute to the regulation of the gene. Loss of heterozygosity studies, using a microsatellite within intron 4 of the LOXL2 gene, revealed that loss of LOXL2 was unlikely to play a major role in either colon or esophageal tumors. These results suggest that increased LOXL2 expression in colon and esophageal cancer may contribute to tumor progression.
Fong
Sheri F T
SF
Cardiovascular Research Center, John A. Burns School of Medicine, University of Hawaii at Manoa, Honolulu, HI 96822, USA. sheri@pbrc.hawaii.edu
Dietzsch
Erin
E
Fong
Keith S K
KS
Hollosi
Peter
P
Asuncion
Lloyd
L
He
Qingping
Q
Parker
M Iqbal
MI
Csiszar
Katalin
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000594:Amino Acid Oxidoreductases / Q000235:genetics*; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D015153:Blotting, Western; D002454:Cell Differentiation / Q000235:genetics*; D002460:Cell Line; D003110:Colonic Neoplasms / Q000201:enzymology* / Q000473:pathology; D018899:CpG Islands; D017931:DNA Primers; D000077209:Decitabine; D004938:Esophageal Neoplasms / Q000201:enzymology* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D019656:Loss of Heterozygosity; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D000077209:Decitabine; D000594:Amino Acid Oxidoreductases; C119091:LOXL2 protein, human; D001374:Azacitidine