Failure to induce inhibition of cyclin A and up-regulation of p21 expression in phorbol ester-resistant U937 cells by phorbol ester

Differentiation resistant U937 cells were derived from parental U937 cells by selecting for continuously growing U937 cells in cell cultures continuou sly exposed to phorbol 12 myristate 13-acetate (PMA), Unlike in other known PMA resistant U937, the basal expression of protein kinase C (PKC) isozyme s in these PMA resistant cells (R-U937) was significantly decreased. Subseq uent analyses revealed differences between the wild type U937 and the R-U93 7 cells with respect to G1 phase arrest, which seemed to occur in U937 beca use of low levels of cdk2 kinase activity. This abolished cdk2 kinase activ ity is mainly due to inhibition of cdk2 phosphorylation, cyclin A down-regu lation and cyclin dependent kinase inhibitor p21 up-regulation. Our data su ggest that events down-stream of PKC activation may mediate cell cycle cont rol. Thus, the R-U937 cells could be useful for further PKC mediated cell c ycle control studies. (C) 2000 Elsevier Science Ireland Ltd. All rights res erved.