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

Qing Mei Wang, George P. Studzinski, Fei Chen, Frederick D. Coffman, Lawrence Harrison

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)238-246
Number of pages9
JournalJournal of Cellular Physiology
Volume183
Issue number2
DOIs
StatePublished - Apr 14 2000
Externally publishedYes

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Calcitriol
HL-60 Cells
S Phase
Oligodeoxyribonucleotides
DNA
Bromodeoxyuridine
Growth
Phosphotransferases
Up-Regulation
Chemical activation
Cells
Cell Proliferation
Messenger RNA
Proteins
Experiments

All Science Journal Classification (ASJC) codes

  • Physiology
  • Clinical Biochemistry
  • Cell Biology

Cite this

Wang, Qing Mei ; Studzinski, George P. ; Chen, Fei ; Coffman, Frederick D. ; Harrison, Lawrence. / p53/56(lyn) antisense shifts the 1,25-dihydroxyvitamin D3-induced G1/S block in HL60 cells to S phase. In: Journal of Cellular Physiology. 2000 ; Vol. 183, No. 2. pp. 238-246.
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p53/56(lyn) antisense shifts the 1,25-dihydroxyvitamin D3-induced G1/S block in HL60 cells to S phase. / Wang, Qing Mei; Studzinski, George P.; Chen, Fei; Coffman, Frederick D.; Harrison, Lawrence.

In: Journal of Cellular Physiology, Vol. 183, No. 2, 14.04.2000, p. 238-246.

Research output: Contribution to journalArticle

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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

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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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