Fatty acid synthase hyperactivation in human colorectal cancer: relationship with tumor side and sex.
OBJECTIVE
Fatty acid synthase (FAS) is a multienzyme protein required for the conversion of acetyl coenzyme A and malonyl coenzyme A to palpitate. High levels of FAS expression have been found in many human cancers, including breast, prostate and colon. In this study, we evaluated FAS activity levels and the expression of its mRNA in normal colorectal mucosa and cancer tissue from patients operated for colorectal carcinoma. In addition, the hypothesis of a relation between FAS activity and p53 mutation status of patients was tested.


METHODS
Forty-two patients were enrolled in the study. FAS activity was measured by using a radiometric assay. FAS gene expression was determined using quantitative reverse-transcription polymerase chain reaction and p53 mutations by polymerase chain reaction single-strand conformation polymorphism.


RESULTS
FAS activity levels were significantly higher in cancer than in the corresponding normal mucosa. Tumors located on the left side of the colon showed higher levels of FAS activity and tumors from male patients showed higher FAS activity than tumors from females. No difference was detected in mRNA FAS levels according to tumor side and gender. Moreover, lower levels of FAS activity were detected in patients carrying the p53 mutation.


CONCLUSIONS
This study suggests that biological factors including sex and gene mutation status, as well as stratification of patients with colorectal cancer into right- and left-sided subsets, may be important in patient selection for targeted therapies and for the subsequent assessment of objective therapeutic responses.
Notarnicola
Maria
M
Laboratory of Biochemistry, National Institute for Digestive Diseases S. de Bellis, Castellana Grotte, Italy.
Altomare
Donato Francesco
DF
Calvani
Menotti
M
Orlando
Antonella
A
Bifulco
Maurizio
M
D'Attoma
Benedetta
B
Caruso
Maria Gabriella
MG
D000368:Aged; D015179:Colorectal Neoplasms / Q000201:enzymology* / Q000235:genetics / Q000473:pathology; D004252:DNA Mutational Analysis; D004789:Enzyme Activation; D064429:Fatty Acid Synthases / Q000235:genetics / Q000378:metabolism*; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology / Q000473:pathology; D008297:Male; D009154:Mutation; D009367:Neoplasm Staging; D012333:RNA, Messenger / Q000096:biosynthesis; D012737:Sex Factors; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics
D012333:RNA, Messenger; D016159:Tumor Suppressor Protein p53; D064429:Fatty Acid Synthases