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 in hematopoietic cells and is thought to play a role in cellular proliferation. 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 show that the mRNA and protein levels of p53/56(lyn) are markedly elevated after 1, 25D(3) treatment, which is accompanied by an increase of p53/56(lyn) kinase activity. We also demonstrate that treatment with p53/56(lyn) antisense oligodeoxynucleotides reverses the 1,25D(3)-induced G1/S block, and results in an accumulation of cells with S-phase DNA content. BrdU pulse-chase experiments reveal that this accumulation results from an increased proportion of cells actively synthesizing DNA, which are inhibited from exiting the S-phase compartment. These results indicate that upregulation of p53/56(lyn) contributes significantly to the G1/S growth arrest induced by 1,25D(3) in HL60 cells and thus its activation may be a desirable outcome of chemotherapeutic regimens.
Wang
Q M
QM
Department of Surgery, UMDNJ-New Jersey Medical School, Newark, NJ 07103, USA.
Studzinski
G P
GP
Chen
F
F
Coffman
F D
FD
Harrison
L E
LE
D001483:Base Sequence; D002117:Calcitriol / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D004247:DNA / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D016193:G1 Phase / Q000187:drug effects*; D015870:Gene Expression / Q000187:drug effects; D018922:HL-60 Cells; D006801:Humans; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics* / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D016196:S Phase / Q000187:drug effects*; D019061:src-Family Kinases / Q000235:genetics* / Q000378:metabolism
D017931:DNA Primers; D020319:Oligodeoxyribonucleotides, Antisense; D012333:RNA, Messenger; D004247:DNA; C060902:lyn protein-tyrosine kinase; D019061:src-Family Kinases; D002117:Calcitriol