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An acidic environment changes cyclin D1 localization and alters colony forming ability in gliomas

  • Lab. Investigation-Human/Animal Tissue
  • Published:
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Abstract

The human glioma cell lines, U87 and T98G, were evaluated for their ability to survive and form colonies in an acidic environment of pHext 6.0. In contrast to U87, which showed an 80–90% survival rate, only 40% of T98G cells survived 6 days at pHext 6.0 and lost their colony forming ability when returned to a normocidic environment. Although both U87 and T98G cells maintain an intracellular pH (pHi) of 7.0 at pHext 6.0 and arrest mostly in G1 phase of the cell cycle, only T98G demonstrated a major loss of cyclin D1 that was prevented by the proteasome inhibitor MG132. Colony forming ability was restored by stably transfecting T98G cells with a cyclin D1-expressing plasmid. Both U87 and T98G cells demonstrated increased cytoplasmic localization of cyclin D1 during exposure at pHext 6.0. Upon prolonged (24 h) incubation at pHext 6.0, nuclear cyclin D1 was nearly absent in T98G in contrast to U87 cells. Thus, an acidic environment triggers cytoplasmic localization and proteasomal degradation of cyclin D1.

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Acknowledgement

This study was supported by grant NIH NS40489 (F.G.), by the University of California Cancer Research Coordinating Committee (F.G.) and by funds from the UC Davis Cancer center (J.S.).

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Author notes

  1. Joachim B. Schnier & Kayoko Nishi

    Present address: Department of Neurology and the Center for Neuroscience, University of California Davis, 1515 Newton Court, Davis, CA, 95618, USA

Authors and Affiliations

  1. Department of Biochemistry and Molecular Medicine, University of California Davis, One Shields Ave, Davis, CA, 95616, USA

    Joachim B. Schnier & Kayoko Nishi

  2. Department of Neurology and the Center for Neuroscience, University of California Davis, 1515 Newton Court, Davis, CA, 95618, USA

    William R. Harley & Fredric A. Gorin

  3. UC Davis National Cancer Center, University of California Davis, Davis, CA, USA

    Joachim B. Schnier & Fredric A. Gorin

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  1. Joachim B. Schnier
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  4. Fredric A. Gorin
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Correspondence to Joachim B. Schnier.

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Schnier, J.B., Nishi, K., Harley, W.R. et al. An acidic environment changes cyclin D1 localization and alters colony forming ability in gliomas. J Neurooncol 89, 19–26 (2008). https://doi.org/10.1007/s11060-008-9591-8

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  • DOI: https://doi.org/10.1007/s11060-008-9591-8

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