Expression of LOX is upregulated under hypoxia in metastatic colorectal carcinoma cells

Abstract

Lysyl oxidase (LOX) is an extracellular amine oxidase catalyzing the formation of lysine-derived cross-linkages in collagen and elastin in the extracellular matrices. Four human paralogs of LOX (LOXL1, LOXL2, LOXL3, and LOXL4) have been identified, each encoding the functional domains required for the amine oxidase activity of LOX. Recently, upregulation of the LOX and LOXL2 expression was reported to be significantly correlated with absence of lymphovascular invasion in tumor tissues from colorectal adenocarcinoma patients, suggesting that the oxygen tension around the tumors may be an important factor for expressional regulation of these genes in colorectal carcinomas. To evaluate the effects of hypoxia on expression of LOX and LOXL2 in colorectal carcinomas, we performed promoter assays and RT-PCR analysis under hypoxia in colorectal carcinoma cell lines, HT-29 and HCT-116. LOX expression was upregulated under hypoxia in both HT-29 and HCT-116 cells, whereas LOXL2 expression was not affected by hypoxia in those cells. In the highly metastatic HCT-116 cells, LOX showed a higher level of upregulation than in HT-29 cells, suggesting that LOX upregulation may be associated with increased invasiveness and metastatic potential in colorectal carcinomas.