Expression of CD26 and its associated dipeptidyl peptidase IV enzyme activity enhances sensitivity to doxorubicin-induced cell cycle arrest at the G(2)/M checkpoint.
CD26, a M(r) 110,000 surface-bound ectopeptidase with dipeptidyl peptidase IV (DPPIV) activity, has an array of diverse functional properties, with a role in T-cell physiology and the development of certain human cancers. In this study, we report that surface expression of CD26, through its associated DPPIV enzyme activity, enhanced sensitivity of Jurkat T-cell transfectants to G(2)-M arrest induced by the chemotherapeutic drug, doxorubicin. This was associated with disruption of cell cycle-related events, including hyperphosphorylation and inhibition of p34(cdc2) kinase activity, phosphorylation of cdc25C, and alteration in cyclin B1 expression. In addition, we demonstrate that the addition of exogenous soluble DPPIV enhanced sensitivity of lymphoid tumor cell lines to doxorubicin, suggesting a potentially useful clinical role for CD26/DPPIV in the treatment of selected human hematological malignancies.
Aytac
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Department of Lymphoma/Myeloma, M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
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Sato
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Morimoto
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D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D016203:CDC2 Protein Kinase / Q000037:antagonists & inhibitors / Q000378:metabolism; D018797:Cell Cycle Proteins / Q000378:metabolism; D019926:Cyclin B / Q000096:biosynthesis; D056744:Cyclin B1; D018819:Dipeptidyl Peptidase 4 / Q000096:biosynthesis* / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology*; D016195:G2 Phase / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D019169:Jurkat Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008938:Mitosis / Q000187:drug effects; D010766:Phosphorylation / Q000187:drug effects; D014162:Transfection; D020687:cdc25 Phosphatases / Q000378:metabolism
D000903:Antibiotics, Antineoplastic; C534699:CCNB1 protein, human; D018797:Cell Cycle Proteins; D019926:Cyclin B; D056744:Cyclin B1; D004317:Doxorubicin; D016203:CDC2 Protein Kinase; C517009:CDC25C protein, human; D020687:cdc25 Phosphatases; D018819:Dipeptidyl Peptidase 4