Novel expression and function of peroxisome proliferator-activated receptor gamma (PPAR gamma) in human neuroblastoma cells

Peroxisome proliferator-activated receptor gamma (PPAR gamma) is a member o f the nuclear receptor superfamily of ligand-dependent transcription factor s that has been shown to play a major role in adipocyte and monocyte/macrop hage differentiation. Recent work has also suggested a role for PPAR gamma in cell cycle control and/or differentiation of other cell types including breast and lung cancer cells. Using reverse transcription-PCR, we now show for the first time that human neuroblastoma (nb) cells express PPAR beta an d -gamma, but not -alpha. Using the LA-N-5 nb cell line, we have determined that the natural PPAR gamma Ligand 15-deoxy-delta prostaglandin J2, as wel l as the synthetic PPAR gamma agonist GW1929, can stimulate the differentia tion of nb cells, as evidenced by the inhibition of cell proliferation, neu rite outgrowth, increased acetylcholinesterase activity, and the reduction of N-myc expression. We have also demonstrated that PPAR gamma is expressed in primary nb and, furthermore, that the expression of this receptor corre lates with the maturational stage of the nb cells. Taken together, these st udies have implicated a role for PPAR gamma in peripheral nerve cell biolog y and suggest that the PPAR gamma signaling pathway is involved in the regu lation of nb cell growth and differentiation.