Evidence map›Paper›PMID 18541021›Full record

ArticleRetrovirology2008

Expression of parathyroid hormone-related protein during immortalization of human peripheral blood mononuclear cells by HTLV-1: implications for transformation.

Murali V P Nadella, Sherry T Shu, Wessel P Dirksen, Nanda K Thudi, Kiran S Nadella, Soledad A Fernandez, Michael D Lairmore, Patrick L Green, Thomas J Rosol

Open access · goldAbstract read
In one paragraph

Article in Retrovirology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed
1.1field-weighted citation impact, top 22% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

13 citing papers in PubMed, 21 citations in OpenAlex.

  1. Epidemiology and Clinical Outcomes of HTLV-1: A Comprehensive Narrative Review of Endemic and Nonendemic Regions.The Canadian journal of infectious diseases & medical microbiology = Journal canadien des maladies infectieuses et de la microbiologie medicale · 2026
    Review
  2. Review
  3. Article
  4. Regulation of HTLV-1 transformation.Bioscience reports · 2022
    Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Review
  13. The HTLV-1 Tax interactome.Retrovirology · 2008
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 2 institutions in 1 country.

Murali V P NadellaDepartment of Veterinary Biosciences, The Ohio State University, Columbus, OH, USA. Thomas.Rosol@cvm.osu.edu
Sherry T Shu
Wessel P Dirksen
Nanda K Thudi
Kiran S Nadella
Soledad A Fernandez
Michael D Lairmore
Patrick L Green
Thomas J Rosol
The Ohio State University · USCancer Genetics (United States) · US

Funding

ZETA CHAIN OF T CELL RECEPTOR INTERACTS W/ NEF OF SIV &HIV2P51RR000168 · NCRR · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI WESTMORELAND, SUSAN V. · 1985 to 2011
$139.3M
Role of Inflammation in Tax-mediated TumorigenesisP01CA100730 · NCI · WASHINGTON UNIVERSITY · PI Malachi Griffith · 2003 to 2026
$44.8M
MOUSE PATHOBIOLOGY: MODELS OF HUMAN DISEASET32RR007073 · NCRR · OHIO STATE UNIVERSITY · PI ROSOL, THOMAS J · 2002 to 2011
$3.2M
PTHRP IN SQUAMOUS CELL CARCINOMA AND TGF BETAR01CA077911 · NCI · OHIO STATE UNIVERSITY · PI ROSOL, THOMAS J · 1998 to 2002
$728k
MOUSE MODELS OF CANCER, BONE DISEASE, AND LACTATIONK26RR000168 · NCRR · OHIO STATE UNIVERSITY · PI ROSOL, THOMAS J · 2000 to 2004
$547k
NCI NIH HHS CA100730NCI NIH HHS CA77911NCI NIH HHS P01 CA100730NCI NIH HHS R01 CA077911NCRR NIH HHS K26 RR000168NCRR NIH HHS P51 RR000168NCRR NIH HHS RR00168NCRR NIH HHS T32 RR007073NCRR NIH HHS T32 RR07073
6 · The paper itself

Abstract

backgroundAdult T-cell leukemia/lymphoma (ATLL) is initiated by infection with human T-lymphotropic virus type-1 (HTLV-1); however, additional host factors are also required for T-cell transformation and development of ATLL. The HTLV-1 Tax protein plays an important role in the transformation of T-cells although the exact mechanisms remain unclear. Parathyroid hormone-related protein (PTHrP) plays an important role in the pathogenesis of humoral hypercalcemia of malignancy (HHM) that occurs in the majority of ATLL patients. However, PTHrP is also up-regulated in HTLV-1-carriers and HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP) patients without hypercalcemia, indicating that PTHrP is expressed before transformation of T-cells. The expression of PTHrP and the PTH/PTHrP receptor during immortalization or transformation of lymphocytes by HTLV-1 has not been investigated.

resultsWe report that PTHrP was up-regulated during immortalization of lymphocytes from peripheral blood mononuclear cells by HTLV-1 infection in long-term co-culture assays. There was preferential utilization of the PTHrP-P2 promoter in the immortalized cells compared to the HTLV-1-transformed MT-2 cells. PTHrP expression did not correlate temporally with expression of HTLV-1 tax. HTLV-1 infection up-regulated the PTHrP receptor (PTH1R) in lymphocytes indicating a potential autocrine role for PTHrP. Furthermore, co-transfection of HTLV-1 expression plasmids and PTHrP P2/P3-promoter luciferase reporter plasmids demonstrated that HTLV-1 up-regulated PTHrP expression only mildly, indicating that other cellular factors and/or events are required for the very high PTHrP expression observed in ATLL cells. We also report that macrophage inflammatory protein-1alpha (MIP-1alpha), a cellular gene known to play an important role in the pathogenesis of HHM in ATLL patients, was highly expressed during early HTLV-1 infection indicating that, unlike PTHrP, its expression was enhanced due to activation of lymphocytes by HTLV-1 infection.

conclusionThese data demonstrate that PTHrP and its receptor are up-regulated specifically during immortalization of T-lymphocytes by HTLV-1 infection and may facilitate the transformation process.

Indexed as

Cell Transformation, ViralCells, CulturedCell SurvivalChemokine CCL3Coculture TechniquesGene Products, taxHumansHuman T-lymphotropic virus 1Leukocytes, MononuclearParathyroid Hormone-Related ProteinReceptor, Parathyroid Hormone, Type 1Time FactorsUp-RegulationChemokine CCL3Gene Products, taxParathyroid Hormone-Related ProteinPTH1R protein, humanReceptor, Parathyroid Hormone, Type 1tax protein, Human T-lymphotrophic virus 1

Identifiers

PMID18541021
PMCPMC2435116
OpenAlexW2143951959

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.