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 Journal Article
| Authors: | Shu, S. T.; Dirksen, W. P.; Lanigan, L. G.; Martin, C. K.; Thudi, N. K.; Werbeck, J. L.; Fernandez, S. A.; Hildreth, B. E.; Rosol, T. J. |
| Article Title: | 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. © 2012 Informa UK, Ltd. |
| Keywords: | controlled study; human tissue; protein expression; human cell; nonhuman; cancer incidence; sensitivity analysis; mouse; animal tissue; apoptosis; gene expression; cell growth; inhibitor of differentiation 1; cd40 ligand; animal experiment; animal model; immunoglobulin enhancer binding protein; in vivo study; antineoplastic activity; in vitro study; carcinogenesis; tumor necrosis factor alpha; gamma interferon; real time polymerase chain reaction; tumor growth; dna binding; lymphocytes; t cell leukemia; apoptosis regulatory protein; leukemia cell line; regulator gene; transcription factor ap 2; macrophage inflammatory protein 1alpha; stat4 protein; death associated protein kinase; parathyroid hormone related protein; cell lines and animal models; cytokine production and paraneoplastic conditions; colecalciferol receptor; receptor activator of nuclear factor kappa b |
| Journal Title: | Leukemia and Lymphoma |
| Volume: | 53 |
| Issue: | 4 |
| ISSN: | 1042-8194 |
| Publisher: | Taylor & Francis Group |
| Date Published: | 2012-04-01 |
| Start Page: | 688 |
| End Page: | 698 |
| Language: | English |
| DOI: | 10.3109/10428194.2011.626883 |
| PROVIDER: | scopus |
| PMCID: | PMC3314295 |
| PUBMED: | 21942940 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 1 May 2012" - "CODEN: LELYE" - "Source: Scopus" |
