Effect of CD26/dipeptidyl peptidase IV on Jurkat sensitivity to G2/M arrest induced by topoisomerase II inhibitors

U. Aytac, K. Sato, T. Yamochi, T. Yamochi, K. Ohnuma, G. B. Mills, C. Morimoto, N. H. Dang

    Research output: Contribution to journalArticle

    15 Scopus citations

    Abstract

    CD26/dipeptidyl peptidase IV (DPPIV) is a surface antigen with multiple functions, including a role in T-cell activation and the development of certain human cancers. We previously demonstrated that CD26/DPPIV enhanced sensitivity of Jurkat cells to doxorubicin. We now show that expression of CD26/DPPIV enhanced sensitivity of CD26 Jurkat transfectants to G2-M arrest mediated by the antineoplastic agent etoposide. The increased sensitivity to etoposide-induced G2-M arrest was associated with disruption of cell cycle-related events, including hyperphosphorylation of p34cdc2 kinase, change in cdc25C expression and phosphorylation, and alteration in cyclin B1 expression. CD26/DPPIV-associated enhancement of doxorubicin and etoposide-induced G2-M arrest was also observed in serum-free media, suggesting an effect of CD26 on cell-derived processes rather than serum-derived factors. Importantly, our work elucidated a potential mechanism for the enhanced susceptibility of CD26-expressing Jurkat cells to the topoisomerase II inhibitors by demonstrating that CD26/DPPIV surface expression was associated with increased topoisomerase II α levels and enhanced enzyme activity. Besides being the first to show a functional association between the multifaceted molecule CD26 and the key cellular protein topoisomerase II α, our studies provide additional evidence of a potential role for CD26 in the treatment of selected malignancies.

    Original languageEnglish (US)
    Pages (from-to)455-462
    Number of pages8
    JournalBritish Journal of Cancer
    Volume88
    Issue number3
    DOIs
    StatePublished - Feb 10 2003

    Keywords

    • CD26/DPPIV
    • Cell cycle
    • G-M
    • Jurkat
    • Topoisomerase II α

    ASJC Scopus subject areas

    • Oncology
    • Cancer Research

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