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

Joachim B. Schnier, Kayoko Nishi, William R. Harley, Fredric A Gorin

Research output: Contribution to journalArticle

6 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)19-26
Number of pages8
JournalJournal of Neuro-Oncology
Volume89
Issue number1
DOIs
StatePublished - Aug 2008

Keywords

  • Acidosis
  • Cyclin D1
  • Glioma
  • pH
  • Proteasome

ASJC Scopus subject areas

  • Clinical Neurology
  • Cancer Research
  • Oncology
  • Neuroscience(all)

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