Transcriptional regulation of the Drosophila proliferating cell nuclear antigen gene and raf proto-oncogene by ursolic acid in Drosophila cultured Kc cells
Choi, T.Y.; Rhee, S.H.; Kim, H.D.; Kim, C.R.; Kang, H.S.; Yoo, M.A.
Korean Journal of Biological Sciences 1(1): 151-155
ISSN/ISBN: 1226-5071 DOI: 10.1080/12265071.1997.9647362
Promoter of the Drosophila proliferating cell nuclear antigen (PCNA) gene contains DRE (Drosophila DNA 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 DRE and demonstrated the DRE/DREF (DRE-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 (3H)thymidine incorporation assays. The IC50 value of anti-proliferative effects of UA in DNA content assays was about 7.5 muM. 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 antitumor activities of UA.