Coordinate up-regulation of low-density lipoprotein receptor and cyclo-oxygenase-2 gene expression in human colorectal cells and in colorectal adenocarcinoma biopsies

Many colorectal cancers have high levels of cyclo-oxygenase 2 (COX-2), an e nzyme that metabolizes the essential fatty acids into prostaglandins. Since the low-density lipoprotein receptor (LDLr) is involved in the uptake of e ssential fatty acids, we studied the effect of LDL on growth and gene regul ation in colorectal cancer cells, DiFi cells grown in lipoprotein deficient sera (LPDS) grew more slowly than cells with LDL. LDLr antibody caused sig nificant inhibition of tumor cell growth but did not affect controls. In ad dition, LDL uptake did not change in the presence of excess LDL, suggesting that Idlr mRNA lacks normal feedback regulation in some colorectal cancers . Analysis of the Idlr mRNA showed that excess LDL in the medium did not ca use downregulation of the message even after 24 hr, The second portion of t he study examined the mRNA expression of Idlr and its co-regulation with co x-2 in normal and tumor specimens from patients with colorectal adenocarcin omas. The ratio of tumor:paired normal mucosa of mRNA expression of Idlr an d of cox-2 was measured in specimens taken during colonoscopy. Idlr and cox -2 transcripts were apparent in I of I carcinomas. There was significant co ordinate up regulation both of Idlr and of cox-2 in 6 of 11 (55%) tumors co mpared with normal colonic mucosa, There was no up-regulation of cox-2 with out concomitant up-regulation of Idlr, These data suggest that the LDLr is abnormally regulated in some colorectal tumors and may play a role in the u p-regulation of cox-2. (C) 1999 Wiley-Liss, Inc.