TY - JOUR
T1 - p53/56(lyn) antisense shifts the 1,25-dihydroxyvitamin D3-induced G1/S block in HL60 cells to S phase
AU - Wang, Qing Mei
AU - Studzinski, George P.
AU - Chen, Fei
AU - Coffman, Frederick D.
AU - Harrison, Lawrence E.
PY - 2000
Y1 - 2000
N2 - 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 D3 (1,25D3)-induced growth arrest in HL60 cells. We show that the mRNA and protein levels of p53/56(lyn) are markedly elevated after 1,25D3 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 1,25D3-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 1,25D3 in HL60 cells and thus its activation may be a desirable outcome of chemotherapeutic regimens. (C) 2000 Wiley-Liss, Inc.
AB - 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 D3 (1,25D3)-induced growth arrest in HL60 cells. We show that the mRNA and protein levels of p53/56(lyn) are markedly elevated after 1,25D3 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 1,25D3-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 1,25D3 in HL60 cells and thus its activation may be a desirable outcome of chemotherapeutic regimens. (C) 2000 Wiley-Liss, Inc.
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U2 - 10.1002/(SICI)1097-4652(200005)183:2<238::AID-JCP10>3.0.CO;2-1
DO - 10.1002/(SICI)1097-4652(200005)183:2<238::AID-JCP10>3.0.CO;2-1
M3 - Article
C2 - 10737899
AN - SCOPUS:0009582439
SN - 0021-9541
VL - 183
SP - 238
EP - 246
JO - Journal of Cellular Physiology
JF - Journal of Cellular Physiology
IS - 2
ER -