1,25-dihydroxyvitamin D3-induced retardation of the G2/M traverse is associated with decreased levels of p34(cdc2) in HL60 cells

Lawrence E. Harrison, Qing Mei Wang, George P. Studzinski

Research output: Contribution to journalArticle

20 Citations (Scopus)

Abstract

Cellular differentiation of neoplastic cells after exposure to 1,25- dihydroxyvitamin D3 (1,25 D3) is accompanied by altered cell cycle regulation. In previous studies, blocks in both G1/S and G2/M checkpoints have been observed in 1,25D3-treated HL60 cells, but the mechanism of the 1,25D3-induced G2/M block has not been previously reported. In this study, we show by cell cycle analysis, using bromodeoxyuridine pulse-chase labeling, that the G2/M block in 1,25D3-treated HL60 cells is incomplete. We also demonstrate that although the 1,25D3-treated cells exhibit elevated levels of cyclin B1, Cdc25C, and Cdk7, which are positive regulators of the G2/M traverse, these cells have decreased protein levels of p34(cdc2) and decreased p34(cdc2) kinase activity. This provides potential mechanisms for the observed accumulation of cells in the G2 cell cycle compartment and occasional polyploidization following treatment of HL60 cells with 1,25D3. The data also suggest that the ability of some cells to traverse this block may be the result of cellular compensatory mechanisms responding to decreased p34(cdc2) activity by increasing the levels of other regulators of the G2 traverse, such as cyclin B1, Cdc25C, and Cdk7.

Original languageEnglish (US)
Pages (from-to)226-234
Number of pages9
JournalJournal of Cellular Biochemistry
Volume75
Issue number2
DOIs
StatePublished - Nov 1 1999
Externally publishedYes

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Calcitriol
HL-60 Cells
Cells
Cyclin B1
Cell Cycle
Bromodeoxyuridine
Cell Differentiation
Phosphotransferases
Labeling
Proteins

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

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title = "1,25-dihydroxyvitamin D3-induced retardation of the G2/M traverse is associated with decreased levels of p34(cdc2) in HL60 cells",
abstract = "Cellular differentiation of neoplastic cells after exposure to 1,25- dihydroxyvitamin D3 (1,25 D3) is accompanied by altered cell cycle regulation. In previous studies, blocks in both G1/S and G2/M checkpoints have been observed in 1,25D3-treated HL60 cells, but the mechanism of the 1,25D3-induced G2/M block has not been previously reported. In this study, we show by cell cycle analysis, using bromodeoxyuridine pulse-chase labeling, that the G2/M block in 1,25D3-treated HL60 cells is incomplete. We also demonstrate that although the 1,25D3-treated cells exhibit elevated levels of cyclin B1, Cdc25C, and Cdk7, which are positive regulators of the G2/M traverse, these cells have decreased protein levels of p34(cdc2) and decreased p34(cdc2) kinase activity. This provides potential mechanisms for the observed accumulation of cells in the G2 cell cycle compartment and occasional polyploidization following treatment of HL60 cells with 1,25D3. The data also suggest that the ability of some cells to traverse this block may be the result of cellular compensatory mechanisms responding to decreased p34(cdc2) activity by increasing the levels of other regulators of the G2 traverse, such as cyclin B1, Cdc25C, and Cdk7.",
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1,25-dihydroxyvitamin D3-induced retardation of the G2/M traverse is associated with decreased levels of p34(cdc2) in HL60 cells. / Harrison, Lawrence E.; Wang, Qing Mei; Studzinski, George P.

In: Journal of Cellular Biochemistry, Vol. 75, No. 2, 01.11.1999, p. 226-234.

Research output: Contribution to journalArticle

TY - JOUR

T1 - 1,25-dihydroxyvitamin D3-induced retardation of the G2/M traverse is associated with decreased levels of p34(cdc2) in HL60 cells

AU - Harrison, Lawrence E.

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AU - Studzinski, George P.

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AB - Cellular differentiation of neoplastic cells after exposure to 1,25- dihydroxyvitamin D3 (1,25 D3) is accompanied by altered cell cycle regulation. In previous studies, blocks in both G1/S and G2/M checkpoints have been observed in 1,25D3-treated HL60 cells, but the mechanism of the 1,25D3-induced G2/M block has not been previously reported. In this study, we show by cell cycle analysis, using bromodeoxyuridine pulse-chase labeling, that the G2/M block in 1,25D3-treated HL60 cells is incomplete. We also demonstrate that although the 1,25D3-treated cells exhibit elevated levels of cyclin B1, Cdc25C, and Cdk7, which are positive regulators of the G2/M traverse, these cells have decreased protein levels of p34(cdc2) and decreased p34(cdc2) kinase activity. This provides potential mechanisms for the observed accumulation of cells in the G2 cell cycle compartment and occasional polyploidization following treatment of HL60 cells with 1,25D3. The data also suggest that the ability of some cells to traverse this block may be the result of cellular compensatory mechanisms responding to decreased p34(cdc2) activity by increasing the levels of other regulators of the G2 traverse, such as cyclin B1, Cdc25C, and Cdk7.

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