Rexinoids Induce Differential Gene Expression in Human Glioblastoma Cells

Rexinoids are compounds that bind to the rexinoid X receptor (RXR) to modulate gene expression and have been proposed as a new class of therapeutics to treat Alzheimer's disease. Different rexinoids will initiate downstream effects that can be quite marked even though such compounds can be structurally similar and have comparable RXR binding affinities. RXR can both homo- and heterodimerize and these protein-protein interactions and subsequent transactivating potential leads to differential gene expression, depending on the RXR dimeric partner, additional cofactors recruited, and downstream transcription factors that are up- or down-regulated. Expression analysis was performed in the U87 human glioblastoma cell line treated with a panel of rexinoids, and our analysis demonstrated that rexinoids with similar RXR EC50 values can have pronounced differences in differential gene expression. Negative control was ethanol, positive control was Bexarotene, and rexinoid compounds were A34, A41, A80, and A98, concentration of 1 X 10-7 M for 24 h treatment (rexinoids synthesized at Arizona State University).