Biochemical changes of mevalonate pathway in human colorectal cancer.
BACKGROUND
Alterations in the mevalonate pathway may contribute to malignant cell growth. There are differences in the aetiology, clinical behaviour, pathological and genetic features in cancer of the right versus the left colon. Here, 3-hydroxy-3-methylglutatyl coenzyme A (HMG-CoA) reductase, farnesylpyrophosphate (FPP) synthase and farnesyltransferase (Ftase) activities were measured in human colorectal cancer (CRC) and normal mucosa in order to evaluate their role as potential markers of malignancy, also in relation to cancer location.


METHODS
HMG-CoA reductase, FPP synthase and Ftase activities were determined in CRC and normal mucosa of 90 patients by radiochemical assay.


RESULTS
The enzymatic activities were higher in cancer than in normal mucosa. The tumours located at the left side showed higher HMG-CoA reductase activity, whereas the right side tumours showed higher levels of Ftase and FPP synthase activity.


CONCLUSIONS
The determination of mevalonate pathway enzymes in relation to CRC location may be clinically relevant in designing anticancer targeted therapies.
Caruso
Maria Gabriella
MG
Laboratory of Biochemistry, National Institute for Digestive Disease, Castellana Grotte, Bari, Italy. irccsbiochimica@libero.it
Notarnicola
Maria
M
D000368:Aged; D019883:Alkyl and Aryl Transferases / Q000378:metabolism*; D014408:Biomarkers, Tumor / Q000378:metabolism; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051231:Farnesyltranstransferase; D005260:Female; D011905:Genes, ras; D051228:Geranyltranstransferase; D006801:Humans; D006903:Hydroxymethylglutaryl CoA Reductases / Q000378:metabolism*; D007413:Intestinal Mucosa / Q000201:enzymology / Q000378:metabolism; D008297:Male; D008798:Mevalonic Acid / Q000378:metabolism*; D008875:Middle Aged; D009154:Mutation
D014408:Biomarkers, Tumor; D006903:Hydroxymethylglutaryl CoA Reductases; D019883:Alkyl and Aryl Transferases; D051228:Geranyltranstransferase; D051231:Farnesyltranstransferase; D008798:Mevalonic Acid