Enhanced 3-hydroxy-3-methyl-glutaryl coenzyme A reductase activity in human colorectal cancer not expressing low density lipoprotein receptor

Background: We have previously shown that 63.3% of colorectal cancer neopla stic specimens did not express the Low Density Lipoprotein Receptor (LDLR) protein and that the absence of LDLR predicted shorter survival. We now rep ort the findings of a preliminary study on HMG-CoA reductase (HMG-CoAR) act ivity in neoplastic tissue specimens of human colorectal cancers (CRC) expr essing or not expressing LDLR. Materials and methods. the tissue specimens were obtained from 16 patients (10 males and 6 females) undergoing surgical resection for CRC, and previously characterized for LDLR (7 not expressing LDLR and 9 expressing LDLR). HMG-CoAR is activity was measured by radioche mical assay using C-14-HMG-CoA as substrate. Results: HMG-CoAR activity was significantly higher in specimens not expressing LDLR than in those expres sing LDLR [8.3 pmol/min/mg prot (2.4-16) vs 3.9 pmol/min/mg prot (1.2-7.8), data expressed as median value and the range, p=0.02 Wilcoxon Rank sum tes t)]. Conclusions: the cholesterol requirement in CRC not expressing LDLR ma y be mel by increasing endogenous synthesis. For this reason, the use of HM G-CoA R inhibitors for the treatment of CRC expressing high HMG-CoAR activi ty-dependence for growth may be clinically important.