Transcriptional regulation of parathyroid hormone-related protein promoter P3 by ETS-1 in adult T-cell leukemia/lymphoma

V. Richard, M. V P Nadella, P. L. Green, M. D. Lairmore, G. Feuer, John Foley, T. J. Rosol

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

Parathyroid hormone-related protein (PTHrP) plays a primary role in the development of humoral hypercalcemia of malignancy seen in the majority of adult T-cell leukemia/lymphoma (ATLL) patients with human T-cell lymphotropic virus type-1 (HTLV-1) infection. HTLV-1 Tax has been shown to complex with ETS-1 and SP1 to transactivate the PTHrP P3 promoter. Previously, we established a SCID/bg mouse model of human ATL with RV-ATL cells and showed that PTHrP expression was independent of Tax. In this study, we report an inverse correlation of PTHrP with tax/rex mRNA in multiple HTLV-1-positive cell lines and RV-ATL cells. Stimulation of Jurkat T cells with PMA/ionomycin upregullated the PTHrP P3 promoter by a previously characterized Ets binding site and also induced protein/DNA complex formation identical to that observed in RV-ATL cells. Further, we provide evidence that cotransfection with ETs-1 and constitutively active Mek-1 in HTLV-1-negative transformed T cells with stimulation by PMA/ionomycin not only resulted in a robust induction of PTHrP P3 but also formed a complex with ETS-1/P3 EBS similar to that in ATLL cells. Our data demonstrate that transcriptional regulation of PTHrP in ATLL cells can be controlled by T-cell receptor signaling and the ETS and MAPK ERK pathway in a Tax-independent manner.

Original languageEnglish
Pages (from-to)1175-1183
Number of pages9
JournalLeukemia
Volume19
Issue number7
DOIs
StatePublished - Jul 2005

Fingerprint

Parathyroid Hormone-Related Protein
Adult T Cell Leukemia Lymphoma
Human T-lymphotropic virus 1
T-Lymphocytes
Ionomycin
Jurkat Cells
SCID Mice
MAP Kinase Signaling System
Virus Diseases
T-Cell Antigen Receptor
Binding Sites
Cell Line
Messenger RNA
DNA

Keywords

  • Adult T-cell leukemia/lymphoma (ATLL)
  • ETS-1
  • HTLV-1
  • Humoral hypercalcemia of malignancy (HHM)
  • Parathyroid hormone-related protein (PTHrP)
  • Transcriptional regulation

ASJC Scopus subject areas

  • Hematology
  • Cancer Research

Cite this

Richard, V., Nadella, M. V. P., Green, P. L., Lairmore, M. D., Feuer, G., Foley, J., & Rosol, T. J. (2005). Transcriptional regulation of parathyroid hormone-related protein promoter P3 by ETS-1 in adult T-cell leukemia/lymphoma. Leukemia, 19(7), 1175-1183. https://doi.org/10.1038/sj.leu.2403787

Transcriptional regulation of parathyroid hormone-related protein promoter P3 by ETS-1 in adult T-cell leukemia/lymphoma. / Richard, V.; Nadella, M. V P; Green, P. L.; Lairmore, M. D.; Feuer, G.; Foley, John; Rosol, T. J.

In: Leukemia, Vol. 19, No. 7, 07.2005, p. 1175-1183.

Research output: Contribution to journalArticle

Richard, V. ; Nadella, M. V P ; Green, P. L. ; Lairmore, M. D. ; Feuer, G. ; Foley, John ; Rosol, T. J. / Transcriptional regulation of parathyroid hormone-related protein promoter P3 by ETS-1 in adult T-cell leukemia/lymphoma. In: Leukemia. 2005 ; Vol. 19, No. 7. pp. 1175-1183.
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