Peroxisome proliferator-activated receptor gamma induces growth arrest and differentiation markers of human colon cancer cells.

摘要

Peroxisome proliferator-activated receptor gamma (PPAR gamma), one of the nuclear receptors expressed in adipose tissue, plays an important role in adipocyte differentiation. In this study, we investigated the expression of PPAR gamma and its role in cellular growth and differentiation in six colon cancer cell lines: HT-29, CaCo-2, SW-480, DLD-1, LoVo, and T-84. All six expressed PPAR gamma mRNA and protein, shown respectively on northern and western blot analyses. Luciferase assay in HT-29 cells, which strongly express PPAR gamma, showed that troglitazone, a selective ligand for PPAR gamma, transactivated the transcription of a peroxisome proliferator response element (PPRE)-driven promoter. Furthermore, troglitazone caused a marked decrease in [3H]thymidine incorporation and G1 cell-cycle arrest determined by flow cytometry. Finally, troglitazone induced expression of mRNAs for villin and intestinal alkaline phosphatase, markers for enterocyte differentiation. In conclusion, human colon cancer cells express PPAR gamma, the ligands of which inhibit cell growth and induce differentiation markers.