Effect of retinoic acid on cell proliferation-related gene expression in Raji cells induced by 12-O-tetra-decanoylphorbol-13-acetate

The Epstein-Barr (EB) virus early antigen expression inhibition test on Raji cells is accepted worldwide as a useful assay system for screening of cancer chemo-preventive agents, and the results obtained with it correlate somewhat with those of in vivo screening by the mouse skin test. In this study, to investigate the mechanism of cancer chemoprevention by retinoic acid, we demonstrated the effect of retinoic acid on gene expression induced in Raji cells by 12-O -tetra-decanoylphorbol-13-acetate by using DNA chip technology. We found significant changes in the levels of 322 mRNA's in the cells. Down-regulated genes numbered 109, and up-regulated ones 213. In addition, we evaluated a large number of genes expressed in Raji cells in response to retinoic acid by using a Cell Signaling Network Database (CSNDB) and thereby extracted 21 interesting genes. The retinoic acid responsiveness of these 21 genes in Raji cells is a new finding. We also found three candidates of signaling pathways through examining the enormous gene expression data. This trial may be invaluable for DNA chip/microarray users because of our new methodology using combined array data and database information.