The effect of body weight on altered expression of nuclear receptors and cyclooxygenase-2 in human colorectal cancers.
BACKGROUND
Epidemiological studies on risk factors for colorectal cancer (CRC) have mainly focused on diet, and being overweight is now recognized to contribute significantly to CRC risk. Overweight and obesity are defined as an excess of adipose tissue mass and are associated with disorders in lipid metabolism. Peroxisome proliferator-activated receptors (PPARs) and retinoid-activated receptors (RARs and RXRs) are important modulators of lipid metabolism and cellular homeostasis. Alterations in expression and activity of these ligand-activated transcription factors might be involved in obesity-associated diseases, which include CRC. Cyclooxygenase-2 (COX-2) also plays a critical role in lipid metabolism and alterations in COX-2 expression have already been associated with unfavourable clinical outcomes in epithelial tumors. The objective of this study is to examine the hypothesis questioning the relationship between alterations in the expression of nuclear receptors and COX-2 and the weight status among male subjects with CRC.


METHODS
The mRNA expression of the different nuclear receptor subtypes and of COX-2 was measured in 20 resected samples of CRC and paired non-tumor tissues. The association between expression patterns and weight status defined as a body mass index (BMI) was statistically analyzed.


RESULTS
No changes were observed in PPAR gamma mRNA expression while the expression of PPAR delta, retinoid-activated receptors and COX-2 were significantly increased in cancer tissues compared to normal colon mucosa (P <or= 0.001). The weight status appeared to be an independent factor, although we detected an increased level of COX-2 expression in the normal mucosa from overweight patients (BMI >or= 25) compared to subjects with healthy BMI (P = 0.002).


CONCLUSIONS
Our findings show that alterations in the pattern of nuclear receptor expression observed in CRC do not appear to be correlated with patient weight status. However, the analysis of COX-2 expression in normal colon mucosa from subjects with a high BMI suggests that COX-2 deregulation might be driven by excess weight during the colon carcinogenesis process.
Delage
Barbara
B
Laboratoire Alimentation et Cancerogenese Colique, Unite de Nutrition et Signalisation Cellulaire, Universite Bordeaux1, France. delage.barbara@laposte.net
Rullier
Anne
A
Capdepont
Maylis
M
Rullier
Eric
E
Cassand
Pierrette
P
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015992:Body Mass Index; D001835:Body Weight; D015179:Colorectal Neoplasms / Q000150:complications / Q000235:genetics*; D051546:Cyclooxygenase 2 / Q000235:genetics*; D015870:Gene Expression; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000150:complications / Q000235:genetics; D050177:Overweight / Q000150:complications / Q000235:genetics; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000235:genetics*; D048348:Reverse Transcription / Q000502:physiology; D012307:Risk Factors
D012333:RNA, Messenger; D018160:Receptors, Cytoplasmic and Nuclear; D051546:Cyclooxygenase 2