expression of pml tumor suppressor in a431 cells reduces cellular growth by inhibiting the egfr expression

our previous studies showed that the promyelocytic leukemia protein, pml, functions as acellular and growth suppressor. transient expression of pml was also found to repress the activity of theepidermal growth factor receptor (egfr) gene promoter. in this study, we have examined the effects ofpml on a431 cells, which express a high level of egfr protein. the pml gene was introduced into thecells using the adenovirus-mediated gene transfer system. western blot analysis on the extracts from thecells expressing pml showed a significant repression in the expression of the egfr protein. the cellswere examined for growth and dna synthesis. the data showed a marked reduction in both growth anddna synthesis rate in the cells expressing pml compared with the control cells. furthermore, incomparison with the controls, the cells expressing pml were found to be more in g1 phase, fewer in sand about the same number in the g2/m phase. these data clearly demonstrated that the repression ofegfr expression in a431 cells by pml was associated with inhibition of cell growth and alteration ofthe cell cycle distribution, suggesting a novel mechanism for the known growth inhibitory effects ofpml.