Effect of retinoic acid on growth and gene expression of human osteosarcoma cell line Saos-2

Abstract

This study was conducted to examine the effect of retinoic acid (RA) on the growth and gene expression of a human osteoblastic osteosarcoma cell line, Saos-2. RA inhibited in a dose-dependent fashion both cell growth and DNA synthesis of the cell line. RA also dose-dependently lowered the c-myc mRNA level in the cells, when the cells were treated for 24 hr with the reagent. Furthermore, production of c-jun mRNA was inhibited by treatment with RA at 10^-7 and 10-⁶M. RA at 10^-5M inhibited the c-jun mRNA level. It was lower than control at 6 h and returned to the control value by 12 h after the initiation of treatment. Indomethacin, a potent inhibitor of cyclooxygenase, eliminated the inhibitory effect of RA on c-myc and c-jun mRNA expression. On the other hand, RA also lowered, in a dose-dependent manner, the level of liver/bone/kidney alkaline phosphatase mRNA. Interestingly, however, RA stimulated transforming growth factor-beta mRNA exprssion in the cells.
The present study suggests that RA functions as a negative regulator for expression of cmyc, c-jun, and liver/bone/kidney alkaline phosphatase genes and as a positive one for expression of the transforming growth factor-beta gene in human osteosarcoma Saos-2 cells.