p53/56(lyn) antisense shifts the 1,25-dihydroxyvitamin D3-induced G1/S block in HL60 cells to S phase

p53/56(lyn) is a member of the src Family that is predominantly expressed i n hematopoietic cells and is thought to play a role in cellular proliferati on. In this study, we demonstrate the participation of p53/56(lyn) in 1,25- dihydroxyvitamin D-3 (1,25D(3))-induced growth arrest in HL60 cells. We sho w that the mRNA and protein levels of p53/56(lyn) are markedly elevated aft er 1,25D(3) treatment, which is accompanied by an increase of p53/56(lyn) k inase activity. WE also demonstrate that treatment with p53/56(lyn) antisen se oligodeoxynucleotides reverses the 1,25D(3)-induced G1/S block, and resu lts in an accumulation of cells with S-phase DNA content. BrdU pulse-chase experiments reveal that this accumulation results from an increased proport ion of cells actively synthesizing DNA, which are inhibited from exiting th e S-phase compartment. These results indicate that upregulation of p53/56(l yn) contributes significantly to the C1/S growth arrest induced by 1,25D(3) in HL60 cells and thus its activation may be a desirable outcome of chemot herapeutic regimens. (C) 2000 Wiley-Liss, Inc.