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Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols
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Studying Cell Cycle-regulated Gene Expression by Two Complementary Cell Synchronization Protocols

Published on: June 6, 2017

Requirement for isoprenoid-dependent posttranslational modifications in the cell-cycle progression of human

O Larsson, M Carlberg

    International Journal of Oncology
    |May 18, 2011
    PubMed

    Insights

    HMG CoA reductase inhibitors block human breast cancer cell growth by halting cell cycle progression. N-linked protein glycosylation, not protein isoprenylation, is identified as the rate-limiting step in this process.

    Area of Science:

    • Biochemistry
    • Cell Biology
    • Cancer Research

    Background:

    • HMG CoA reductase inhibitors impact cell growth.
    • The precise mechanism of cell cycle arrest by these inhibitors in breast cancer cells requires further elucidation.
    • Distinguishing the roles of protein isoprenylation and glycosylation in cell cycle regulation is crucial.

    Purpose of the Study:

    • To investigate the cell cycle-specific effects of HMG CoA reductase inhibitors on the MDA231 human breast cancer cell line.
    • To determine whether protein isoprenylation or N-linked protein glycosylation is rate-limiting for G1-progression.
    • To elucidate the role of isoprenoid metabolism in regulating the cell cycle of breast cancer cells.

    Main Methods:

    • Treatment of MDA231 cells with 25-hydroxycholesterol and mevinolin.
    • Assessment of cell cycle progression and inhibition.
    • Measurement of glucosamine incorporation to assess N-linked glycosylation.
    • Measurement of mevalonate incorporation to assess protein isoprenylation.
    • Treatment with tunicamycin and trans-trans farnesol.

    Main Results:

    • 25-hydroxycholesterol and mevinolin inhibited MDA231 cell growth by blocking G1 progression.
    • 25-hydroxycholesterol inhibited N-linked glycosylation but not protein isoprenylation.
    • Tunicamycin, an N-linked glycosylation inhibitor, mimicked the G1-progression block.
    • Trans-trans farnesol, an isoprenylation inhibitor, did not affect cell growth.

    Conclusions:

    • N-linked protein glycosylation is rate-limiting for G1-progression in the isoprenoid-regulated cell cycle of human breast cancer cells.
    • Targeting N-linked glycosylation may represent a therapeutic strategy for breast cancer.
    • This study clarifies the distinct roles of protein modifications in cancer cell proliferation.

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