DIFFERENTIATION AND REVERSAL OF MALIGNANT CHANGES IN COLON-CANCER THROUGH PPAR-GAMMA

PPAR gamma is a nuclear receptor that has a dominant regulatory role i n differentiation of cells of the adipose lineage, and has recently be en shown to be expressed in the colon. We show here that PPAR gamma is expressed at high levels in both well- and poorly-differentiated aden ocarcinomas, in normal colonic mucosa and in human colon cancer cell l ines. Ligand activation of this receptor in colon cancer cells causes a considerable reduction in linear and clonogenic growth, increased ex pression of carcinoembryonic antigen and the reversal of many gene exp ression events specifically associated with colon cancer. Transplantab le tumors derived from human colon cancer cells show a significant red uction of growth when mice are treated with troglitazone, a PPAR gamma ligand. These results indicate that the growth and differentiation of colon cancer cells can be modulated through PPAR gamma.