Colonic polyps of acromegalic patients are not associated with mutations of the peroxisome proliferator activated receptor γ gene

Peroxisome proliferator activated receptor (PPAR)γ plays a pivotal role in regulating adipocyte differentiation and metabolism, but also has an antiproliferative effect in several tissues, including colonic mucosa, where it is highly expressed. Loss-of-function mutations have been reported in about 10% of sporadic primary colon cancer. Acromegalic patients have an increased prevalence of colonic neoplasms and lower PPARγ levels in the colonic mucosa. Thus, PPARγ may act as a tumor suppressor gene, and its reduced expression or loss-of-function mutations may contribute to tumorigenesis. In this study the expression and mutations of the PPARγ gene in the colonic polyps and mucosa outside polyps were investigated in 10 acromegalic and 17 non-acromegalic patients. PPARγ expression was evaluated by RT-PCR. PPARγ was expressed in each sample, but expression appeared to be lower in polyps than in mucosa outside polyps from either acromegalic or non-acromegalic patients. All exons of the PPARγ gene were directly sequenced after PCR amplification: no mutations were found either in acromegalic or in non-acromegalic patients. In conclusion, the results of this preliminary study suggest that the lower expression of PPARγ rather than somatic mutations of this gene is involved in colonic tumorigenesis.