Transcriptional Regulation of the Drosophila Proliferating Cell Nuclear Antigen Gene and raf Proto-oncogene by Ursolic Acid in Drosophila Cultured Kc Cells

摘要

Promoter of the Drosophila proliferating cell nuclear antigen (PCNA) gene contains ORE (Drosophila DMA replication-related element) required for the high level expression of replication-related genes. Recently, we found that promoter region of the D-raf (a Drosophila homolog of the human c-raf-1) contains two sequences homologous to the ORE and demonstrated the DRE/DREF (ORE-binding factor) involvement in regulation of the D-raf gene. In this study, using ursolic acid (UA), a pentacyclic triterpene acid reported to possess antitumor activities, we examined effects of UA on proliferation of the Drosophila cultured Kc cells and on expression of the PCNA and D-raf genes. UA showed an inhibitory effect on proliferation of the Kc cells in a concentration-dependent manner in DNA content assays and pHlthymidine incorporation assays. The IC_(50) value of anti-proliferative effects of UA in DNA content assays was about 7.5 mu M. UA showed inhibitory effects on, expression of the PCNA as well as on that of the D-raf, which were examined with the reporter plasmid p5'-168DPCNACAT or p5'-878DrafCAT, respectively. The results obtained in the present study suggest that expression of the PCNA and D-raf genes is coordinately regulated in at least UA-treated Kc cells and that down-regulation of expression of the PCNA and D-raf genes might be related with the anti-tumor activities of UA.