Differential expression of the LOX family genes in human colorectal adenocarcinomas.
Lysyl oxidase (LOX) is an amine oxidase that catalyzes the cross-linking of collage or elastin in the extracellular matrix, regulating the tensile strength and structural integrity of connective tissues. Recently, four paralogues (LOXL, LOXL2, LOXL3 and LOXL4) of LOX have been identified in humans, each containing the functional domains required for the amine oxidase activity toward collagen and elastin. Paradoxical roles of the LOX family members have been reported in various neoplastic tissues as tumor suppressors or promoters depending on tumor status and type. To address expression of the LOX family genes in colorectal adenocarcinomas, we performed real-time PCR analysis with matched tumor/normal tissue specimens from 104 patients. The expression of the LOX family genes was not statistically associated with tumor location, stage, growth type, or differentiation status. However, upregulation of LOX, LOXL2 and LOXL4 was significantly correlated with absence of lymphovascular invasion (P=0.012, 0.014 and 0.005, respectively), suggesting that the oxygen tension in or around the tumors may be an important regulator for the differential expression of LOX, LOXL2 and LOXL4 in colorectal cancer. Additionally, expression of LOX, but not the other LOX family genes, was significantly upregulated in patients with a diffuse cytoplasmic expression pattern of CEA, indicating that LOX upregulation may be associated with increased invasiveness and metastatic potential in colorectal cancer.
Kim
Youngho
Y
Department of Biochemistry, School of Medicine, Wonkwang University, Iksan-City, Jeollabuk-Do 570-749, Korea. youngkim@wku.ac.kr
Roh
Seonae
S
Park
Jung-Young
JY
Kim
Yangsik
Y
Cho
Dong Hyung
DH
Kim
Jin Cheon
JC
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000594:Amino Acid Oxidoreductases / Q000096:biosynthesis / Q000235:genetics*; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000473:pathology; D005260:Female; D015870:Gene Expression; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness / Q000235:genetics; D009367:Neoplasm Staging; D008249:Protein-Lysine 6-Oxidase; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015854:Up-Regulation
D000594:Amino Acid Oxidoreductases; C445313:LOXL1 protein, human; C119091:LOXL2 protein, human; C435668:LOXL3 protein, human; C445682:LOXL4 protein, human; D008249:Protein-Lysine 6-Oxidase