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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 GB, Morimoto C, Dang NH - Br. J. Cancer (2003)

Bottom Line: 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 G(2)-M arrest mediated by the antineoplastic agent etoposide.The increased sensitivity to etoposide-induced G(2)-M arrest was associated with disruption of cell cycle-related events, including hyperphosphorylation of p34(cdc2) kinase, change in cdc25C expression and phosphorylation, and alteration in cyclin B1 expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX 77030, USA.

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 G(2)-M arrest mediated by the antineoplastic agent etoposide. The increased sensitivity to etoposide-induced G(2)-M arrest was associated with disruption of cell cycle-related events, including hyperphosphorylation of p34(cdc2) kinase, change in cdc25C expression and phosphorylation, and alteration in cyclin B1 expression. CD26/DPPIV-associated enhancement of doxorubicin and etoposide-induced G(2)-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 alpha 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 alpha, our studies provide additional evidence of a potential role for CD26 in the treatment of selected malignancies.

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Effect of CD26/DPPIV expression on p34cdc2/cyclin B1 complex and cdc25C following etoposide treatment. Jurkat cells were incubated for 24 h at 37°C with media containing etoposide at the indicated doses. Cells were then harvested, and immunoblotting studies were performed with appropriate antibodies as described in Materials and Methods.
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fig3: Effect of CD26/DPPIV expression on p34cdc2/cyclin B1 complex and cdc25C following etoposide treatment. Jurkat cells were incubated for 24 h at 37°C with media containing etoposide at the indicated doses. Cells were then harvested, and immunoblotting studies were performed with appropriate antibodies as described in Materials and Methods.

Mentions: To elucidate the mechanisms involved in CD26/DPPIV-associated enhancement in etoposide-induced G2–M arrest, we evaluated the status of key regulators of this checkpoint (Figure 3Figure 3


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 GB, Morimoto C, Dang NH - Br. J. Cancer (2003)

Effect of CD26/DPPIV expression on p34cdc2/cyclin B1 complex and cdc25C following etoposide treatment. Jurkat cells were incubated for 24 h at 37°C with media containing etoposide at the indicated doses. Cells were then harvested, and immunoblotting studies were performed with appropriate antibodies as described in Materials and Methods.
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2747550&req=5

fig3: Effect of CD26/DPPIV expression on p34cdc2/cyclin B1 complex and cdc25C following etoposide treatment. Jurkat cells were incubated for 24 h at 37°C with media containing etoposide at the indicated doses. Cells were then harvested, and immunoblotting studies were performed with appropriate antibodies as described in Materials and Methods.
Mentions: To elucidate the mechanisms involved in CD26/DPPIV-associated enhancement in etoposide-induced G2–M arrest, we evaluated the status of key regulators of this checkpoint (Figure 3Figure 3

Bottom Line: 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 G(2)-M arrest mediated by the antineoplastic agent etoposide.The increased sensitivity to etoposide-induced G(2)-M arrest was associated with disruption of cell cycle-related events, including hyperphosphorylation of p34(cdc2) kinase, change in cdc25C expression and phosphorylation, and alteration in cyclin B1 expression.

View Article: PubMed Central - PubMed

Affiliation: Department of Lymphoma/Myeloma, MD Anderson Cancer Center, Houston, TX 77030, USA.

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 G(2)-M arrest mediated by the antineoplastic agent etoposide. The increased sensitivity to etoposide-induced G(2)-M arrest was associated with disruption of cell cycle-related events, including hyperphosphorylation of p34(cdc2) kinase, change in cdc25C expression and phosphorylation, and alteration in cyclin B1 expression. CD26/DPPIV-associated enhancement of doxorubicin and etoposide-induced G(2)-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 alpha 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 alpha, our studies provide additional evidence of a potential role for CD26 in the treatment of selected malignancies.

Show MeSH
Related in: MedlinePlus