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 neoplastic specimens did not express the Low Density Lipoprotein Receptor (LDLR) protein and that the absence of LDLR predicted shorter survival. We now report the findings of a preliminary study on HMG-CoA reductase (HMG-CoAR) activity in neoplastic tissue specimens of human colorectal cancers (CRC) expressing or not expressing LDLR.


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 activity was measured by radiochemical assay using 14C-HMG-CoA as substrate.


RESULTS
HMG-CoAR activity was significantly higher in specimens not expressing LDLR than in those expressing 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 test)].


CONCLUSIONS
The cholesterol requirement in CRC not expressing LDLR may be met by increasing endogenous synthesis. For this reason, the use of HMG-CoA R inhibitors for the treatment of CRC expressing high HMG-CoAR activity-dependence for growth may be clinically important.
Caruso
M G
MG
Laboratorio di Biochimica, IRCCS S. de Bellis, Castellana Grotte, BA, Italy.
Notarnicola
M
M
Santillo
M
M
Cavallini
A
A
Di Leo
A
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002784:Cholesterol / Q000097:blood; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000473:pathology; D005260:Female; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011973:Receptors, LDL / Q000032:analysis*
D011973:Receptors, LDL; D002784:Cholesterol; D006903:Hydroxymethylglutaryl CoA Reductases