EXPRESSION OF THE LOW-DENSITY-LIPOPROTEIN RECEPTOR, HMG-COA REDUCTASE, AND MULTIDRUG-RESISTANCE (MDR1) GENES IN COLORECTAL CARCINOMAS

Some malignant cells have elevated uptake of plasma low-density lipopr otein (LDL). We determined the expressions in colorectal cancers of th e LDL receptor gene, of the gene for the rate-limiting enzyme in chole sterol synthesis, 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) redu ctase, and of the multidrug resistance gene (mdr1) by quantitative RNA -RNA solution hybridisation. LDL receptor RNA levels in tumor tissue e xceeded those in normal mucosa in 20 of 23 patients (2-11-fold higher in 17 of 23 patients), with a mean +/- SD of 7.8 +/- 5.8 copies/cell i n tumor tissue vs 3.5 +/- 2.5 in normal mucosa (P = 0.002). The HMG-Co A reductase gene was similarly expressed in tumor and normal tissue, w ith means and SD of 2.0 +/- 1.3 copies/cell versus 2.2 +/- 1.9 (n = 21 ). Mdr1 RNA was undetectable (<0.15 copies/cell) in 5 of 20 tumors, wi th a mean +/- SD of 1.0 +/- 1.1 copies/cell vs 1.6 +/- 1.7 in normal m ucosa. Expression of all three genes was, in most cases, higher in nor mal liver than in liver metastasis of colorectal carcinomas or normal colon mucosa. The results may form the basis for using LDL as a drug c arrier for treatment of colorectal carcinomas, and may indicate that d rug resistance in these tumors is not due to overexpression of the mdr 1 gene.