Abstract:
:Parathyroid hormone-related protein (PTHrP) and macrophage inflammatory protein-1α (MIP-1α) have been implicated in the pathogenesis of adult T-cell leukemia/lymphoma, but their effects on T-cells have not been well studied. Here we analyzed the functions of PTHrP and MIP-1α on T-cell growth and death both in vitro and in vivo by overexpressing either factor in human Jurkat T-cells. PTHrP or MIP-1α did not affect Jurkat cell growth in vitro, but PTHrP increased their sensitivity to apoptosis. Importantly, PTHrP and MIP-1α decreased both tumor incidence and growth in vivo. To investigate possible mechanisms, polymerase chain reaction (PCR) arrays and real-time reverse transcription (RT)-PCR assays were performed. Both PTHrP and MIP-1α increased the expression of several factors including signal transducer and activator of transcription 4, tumor necrosis factor α, receptor activator of nuclear factor κB ligand and death-associated protein kinase 1, and decreased the expression of inhibitor of DNA binding 1, interferon γ and CD40 ligand in Jurkat cells. In addition, MIP-1α also increased the expression of transcription factor AP-2α and PTHrP increased expression of the vitamin D3 receptor. These data demonstrate that PTHrP and MIP-1α exert a profound antitumor effect presumably by increasing the sensitivity to apoptotic signals through modulation of transcription and apoptosis factors in T-cells.
journal_name
Leuk Lymphomajournal_title
Leukemia & lymphomaauthors
Shu ST,Dirksen WP,Lanigan LG,Martin CK,Thudi NK,Werbeck JL,Fernandez SA,Hildreth BE 3rd,Rosol TJdoi
10.3109/10428194.2011.626883subject
Has Abstractpub_date
2012-04-01 00:00:00pages
688-98issue
4eissn
1042-8194issn
1029-2403journal_volume
53pub_type
杂志文章abstract::The relation between resistance to anticancer drugs and resistance to apoptosis has been investigated in the human leukemic cell line(KY-821) and its drug-resistant sublines. Under serum depletion conditions, drug-resistant cell lines showed apoptotic resistance when compared with the parental cell line. Drug resistan...
journal_title:Leukemia & lymphoma
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journal_title:Leukemia & lymphoma
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