Effects of parathyroid hormone-related protein and macrophage inflammatory protein-1α in Jurkat T-cells on tumor formation in vivo and expression of apoptosis regulatory genes in vitro.

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.

• Authors: Sherry T Shu, Wessel P Dirksen, Lisa G Lanigan, Chelsea K Martin, Nanda K Thudi, Jillian L Werbeck, Soledad A Fernandez, Blake E Hildreth 3rd, Thomas J Rosol
• Journal: Leukemia & lymphoma (Leuk Lymphoma) Vol. 53 Issue 4 Pg. 688-98 (Apr 2012) ISSN: 1029-2403 [Electronic] United States
• PMID: 21942940 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Apoptosis Regulatory Proteins
• Chemokine CCL3
• Parathyroid Hormone-Related Protein
• RANK Ligand
• STAT4 Transcription Factor
• Tumor Necrosis Factor-alpha
• CD40 Ligand
• Interferon-gamma
• DAPK1 protein, human
• Dapk1 protein, mouse
• Death-Associated Protein Kinases
• Calcium-Calmodulin-Dependent Protein Kinases

Topics

• Animals
• Apoptosis (genetics)
• Apoptosis Regulatory Proteins (genetics)
• CD40 Ligand (genetics)
• Calcium-Calmodulin-Dependent Protein Kinases (genetics)
• Cell Line, Tumor
• Chemokine CCL3 (genetics)
• Death-Associated Protein Kinases
• Gene Expression Regulation, Leukemic
• Humans
• Interferon-gamma (genetics)
• Jurkat Cells
• Leukemia, Experimental (genetics, pathology)
• Leukemia, T-Cell (genetics, pathology)
• Male
• Mice
• Mice, Inbred NOD
• Mice, SCID
• Oligonucleotide Array Sequence Analysis
• Parathyroid Hormone-Related Protein (genetics)
• RANK Ligand (genetics)
• Reverse Transcriptase Polymerase Chain Reaction
• STAT4 Transcription Factor (genetics)
• T-Lymphocytes (metabolism, pathology)
• Transplantation, Heterologous
• Tumor Necrosis Factor-alpha (genetics)