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Over-expression of insulin-like growth factor binding protein-related protein-1(IGFBP-rP1/mac25) in the M12 prostate cancer cell line alters tumor growth by a delay in G1 and cyclin A associated apoptosis

Oncogene volume 21, pages 140–147 (2002)Cite this article

Abstract

In the present study, we examined the effects of over-expression of the potential tumor suppressor gene IGFBP-rP1/mac25 on cell-cycle kinetics in prostate cancer cells. The majority of the high expressing IGFBP-rP1/mac25 cell population was located in the G1 and sub-G0/G1 peaks; synchronizing cells in G2/M with nocodazole demonstrated the high expressing IGFBP-rP1/mac25 clones were delayed in the G1 phase of the cell cycle. Unscheduled expression of cyclin A in the sub-G0/G1 peak occurred in the IGFBP-rP1/mac25 clones. Immunoblots showed decreased cyclin D1 and p21 and increased cyclin E, p16, and p27 in the high expressing IGFBP-rP1/mac25 clones compared to the control cells. Cyclin D1/cdk-4,6 and cyclin E/cdk-2 kinase activities decreased but cyclin A/cdk-2 kinase activity increased for the high expressing IGFBP-rP1/mac25 clones compared to control cells. A pRb immunoprecipitation demonstrated more binding of E2F-1 to pRb in the high expressing IGFBP-rP1/mac25 clones than in control cells. Finally, cell senescence, as assessed by senescence-associated β–galactosidase, demonstrated significantly more staining in the IGFBP-rP1/mac25 cells than control cells. These results suggest that IGFBP-rP1/mac25 alters the cell cycle kinetics of the M12 prostate cell line by delaying the cells in the G1 phase of the cell cycle. In addition, the appearance of cyclin A in the sub-G0/G1 phase of the cell cycle and the increased kinase activity of cyclin A/cdk-2 in the IGFBP-rP1/mac25 clones suggests that cyclin A is associated with the apoptotic cells.

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Acknowledgements

We gratefully acknowledge the assistance of Dr Anthony Bakke (OHSU, Portland, Oregon) in evaluating the flow cytometry studies and Drs Ron Rosenfeld and Vivian Hwa (OHSU, Portland, Oregon) for their helpful criticisms. Supported by Veterans Affairs Merit Review Program, VA-DOD, and NIH DK52683 to SR Plymate.

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Authors and Affiliations

  1. Geriatric Research Education and Clinical Center, VAPSHCS, Seattle/Tacoma, 98493, Washington, WA, USA

    Cynthia C Sprenger & Stephen R Plymate

  2. Molecular and Cellular Biology Program, University of Washington, Seattle, 98195, Washington, WA, USA

    Cynthia C Sprenger & Mary E Vail

  3. Department of Urology, Madigan Army Medical Center, Tacoma, 98433, Washington, WA, USA

    Karen Evans

  4. Department of Pathology, Madigan Army Medical Center, Tacoma, 98433, Washington, WA, USA

    Jerry Simurdak

  5. Department of Medicine, University of Washington, Seattle, 98165, Washington, WA, USA

    Stephen R Plymate

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  1. Cynthia C Sprenger
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Correspondence to Stephen R Plymate.

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Sprenger, C., Vail, M., Evans, K. et al. Over-expression of insulin-like growth factor binding protein-related protein-1(IGFBP-rP1/mac25) in the M12 prostate cancer cell line alters tumor growth by a delay in G1 and cyclin A associated apoptosis. Oncogene 21, 140–147 (2002). https://doi.org/10.1038/sj.onc.1205021

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