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Molecular Pharmacology

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Research ArticleArticle

G1 Phase-Dependent Expression of Bcl-2 mRNA and Protein Correlates with Chemoresistance of Human Cancer Cells

Gui Gao and Q. Ping Dou
Molecular Pharmacology November 2000, 58 (5) 1001-1010; DOI: https://doi.org/10.1124/mol.58.5.1001
Gui Gao
Drug Discovery Program, H. Lee Moffitt Cancer Center and Research Institute, and Department of Biochemistry and Molecular Biology, College of Medicine, University of South Florida, Tampa, Florida
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Q. Ping Dou
Drug Discovery Program, H. Lee Moffitt Cancer Center and Research Institute, and Department of Biochemistry and Molecular Biology, College of Medicine, University of South Florida, Tampa, Florida
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Abstract

Recent experiments suggest an interconnection between cell proliferation and programmed cell death (apoptosis), although the detailed molecular mechanisms remain unclear. We have hypothesized that expression of some apoptosis regulators is cell cycle-dependent, which in turn influences tumor cell chemosensitivity in a cell cycle-dependent fashion. To test these hypotheses, we synchronized human leukemia Jurkat T, Neo (using aphidicolin), breast cancer MCF-7, normal fibroblast, and simian virus 40-transformed cells (by aphidicolin or serum starvation), and measured levels of several Bcl-2 family proteins. The highest expression of Bcl-2 protein was found in the G1 phase of all the five cell lines tested. In contrast, levels of Bax protein remained relatively unchanged in four of the cell lines, and levels of Bcl-XL, Bcl-XS, and Bak proteins showed little or no cell cycle-dependent changes in Jurkat T cells. Similar to the changes in Bcl-2 protein levels, its mRNA expression was also G1phase-specific, whereas the level of a Bcl-2 cleavage activity remained constitutive. When treated with an anticancer drug (etoposide or cisplatin) or the kinase inhibitor staurosporin, the cells containing a high G1 population and a high Bcl-2 protein level were much more resistant to the induced apoptosis than the cells containing a high S phase population and a low Bcl-2 protein level. Constitutive overexpression of Bcl-2 protein in Jurkat T cells completely blocked the S phase-associated sensitivity to these apoptosis stimuli. The cell cycle-dependent Bcl-2 protein expression seems to contribute to the regulation of chemosensitivity and apoptotic commitment of human tumor cells.

Footnotes

    • Received February 4, 2000.
    • Accepted July 17, 2000.
  • Send reprint requests to: Dr. Q. Ping Dou, Drug Discovery Program, H. Lee Moffitt Cancer Center and Research Institute, and Department of Biochemistry and Molecular Biology, College of Medicine, University of South Florida, 12902 Magnolia Dr., Tampa, FL 33612-9497. E-mail: douqp{at}moffitt.usf.edu

  • This work is supported in part by a National Institutes of Health Grant AG13300 and a research fund from H. Lee Moffitt Cancer Center & Research Institute (to Q.P.D.), and by the Flow Cytometry, Molecular Biology and Molecular Imaging Core Facilities at H. Lee Moffitt Cancer Center & Research Institute.

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Molecular Pharmacology: 58 (5)
Molecular Pharmacology
Vol. 58, Issue 5
1 Nov 2000
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Research ArticleArticle

G1 Phase-Dependent Expression of Bcl-2 mRNA and Protein Correlates with Chemoresistance of Human Cancer Cells

Gui Gao and Q. Ping Dou
Molecular Pharmacology November 1, 2000, 58 (5) 1001-1010; DOI: https://doi.org/10.1124/mol.58.5.1001

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Research ArticleArticle

G1 Phase-Dependent Expression of Bcl-2 mRNA and Protein Correlates with Chemoresistance of Human Cancer Cells

Gui Gao and Q. Ping Dou
Molecular Pharmacology November 1, 2000, 58 (5) 1001-1010; DOI: https://doi.org/10.1124/mol.58.5.1001
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