STIMULATION OF THE EXPRESSION OF RHOB CONTRIBUTES TO THE ABILITY OF AZATYROSINE TO CONVERT C-ERBB-2-TRANSFORMED CELLS TO A NORMAL MORPHOLOGY

We have reported recently that azatyrosine inhibits the growth of ras- , raf-, or c-erbB-2 transformed NIH3T3 cells and converts the transfor med cells to cells with normal morphology. We show in this study that treatment of c-evbB-2-transformed cells with azatyrosine restore the c apacity for the formation of actin stress fibers, which is closely ass ociated with the phenotype of normal cells. Azatyrosine also restored the expression of the rhoB gene, the product of which regulates the fo rmation of actin stress fibers. To investigate the roll of expression of rhoB in the morphological reversion, c-erbB-2 transformed cells wer e transfected with a rhoB expression vector. The cells that overexpres sed rhoB were flatter than the parental transformed cells and the form ation of actin stress fibers was observed in these flatter cells. Furt hermore, the growth rate of these cells was lower than that of parenta l cells, although the flatter cells were still able to grow anchorage- independently. These results suggest that expression of rhoB is involv ed in the conversion of c-erbB-2-transformed cells to a normal phenoty pe that is induced by azatyrosine, but such expression is insufficient by itself for complete reversion.