ArticleLeukemia2007
Transcriptional regulation of parathyroid hormone-related protein promoter P2 by NF-kappaB in adult T-cell leukemia/lymphoma.
Article in Leukemia, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed.
- Review
- Article
- Can the calcium-regulating hormones counteract the detrimental impact of pro-inflammatory damage-associated molecular patterns in the development of heart failure?Journal of investigative medicine : the official publication of the American Federation for Clinical Research · 2021Review
- Circadian clock dysfunction in human omental fat links obesity to metabolic inflammation.Nature communications · 2021Article
- In Vivo Tumorigenesis, Osteolytic Sarcomas, and Tumorigenic Cell Lines from Transgenic Mice Expressing the Human T-Lymphotropic Virus Type 1 (HTLV-1) Tax Viral Oncogene.The American journal of pathology · 2021Article
- Mouse model recapitulates the phenotypic heterogeneity of human adult T-cell leukemia/lymphoma in bone.Journal of bone oncology · 2019Article
- Osteolytic bone resorption in adult T-cell leukemia/lymphoma.Leukemia & lymphoma · 2010Article
- Expression of parathyroid hormone-related protein during immortalization of human peripheral blood mononuclear cells by HTLV-1: implications for transformation.Retrovirology · 2008Article
- A novel bioluminescent mouse model and effective therapy for adult T-cell leukemia/lymphoma.Cancer research · 2007Article
- Molecular aspects of HTLV-I infection and adult T-cell leukaemia/lymphoma.Journal of clinical pathology · 2007Review
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
Parathyroid hormone-related protein (PTHrP) plays a primary role in the development of humoral hypercalcemia of malignancy (HHM) that occurs in the majority of patients with adult T-cell leukemia/lymphoma (ATLL) due to human T-cell lymphotropic virus type-1 (HTLV-1) infection. We previously showed that ATLL cells constitutively express high levels of PTHrP via activation of promoters P2 and P3, resulting in HHM. In this study, we characterized a nuclear factor-kappaB (NF-kappaB) binding site in the P2 promoter of human PTHrP. Using electrophoretic mobility shift assays, we detected a specific complex in Tax-expressing human T cells composed of p50/c-Rel, and two distinct complexes in ATLL cells consisting of p50/p50 homodimers and a second unidentified protein(s). Chromatin immunoprecipitation assays confirmed in vivo binding of p50 and c-Rel on the PTHrP P2 promoter. Using transient co-transfection with NF-kappaB expression plasmids and PTHrP P2 luciferase reporter-plasmid, we showed that NF-kappaB p50/p50 alone and p50/c-Rel or p50/Bcl-3 cooperatively upregulated the PTHrP P2 promoter. Furthermore, inhibition of NF-kappaB activity by Bay 11-7082 reduced PTHrP P2 promoter-initiated transcripts in HTLV-1-infected T cells. In summary, the data demonstrated that transcriptional regulation of PTHrP in ATLL cells can be controlled by NF-kappaB activation and also suggest a Tax-independent mechanism of activation of PTHrP in ATLL.
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Registered trials
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