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, Gordon Mills, C. Morimoto, N. H. Dang

Research output: Contribution to journalArticle

14 Citations (Scopus)

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
Externally publishedYes

Fingerprint

Topoisomerase II Inhibitors
Dipeptidyl Peptidase 4
Etoposide
Type II DNA Topoisomerase
Jurkat Cells
Doxorubicin
Cyclin B1
Serum-Free Culture Media
Human Development
Surface Antigens
Antineoplastic Agents
Neoplasms
Cell Cycle
Phosphotransferases
Phosphorylation
T-Lymphocytes
Enzymes
Serum
Proteins

Keywords

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

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Effect of CD26/dipeptidyl peptidase IV on Jurkat sensitivity to G2/M arrest induced by topoisomerase II inhibitors. / Aytac, U.; Sato, K.; Yamochi, T.; Yamochi, T.; Ohnuma, K.; Mills, Gordon; Morimoto, C.; Dang, N. H.

In: British Journal of Cancer, Vol. 88, No. 3, 10.02.2003, p. 455-462.

Research output: Contribution to journalArticle

Aytac, U. ; Sato, K. ; Yamochi, T. ; Yamochi, T. ; Ohnuma, K. ; Mills, Gordon ; Morimoto, C. ; Dang, N. H. / Effect of CD26/dipeptidyl peptidase IV on Jurkat sensitivity to G2/M arrest induced by topoisomerase II inhibitors. In: British Journal of Cancer. 2003 ; Vol. 88, No. 3. pp. 455-462.
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