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Selection against puma gene expression in myc-driven b-cell lymphomagenesis

Academic Article
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Overview

authors

  • Garrison, S. P.
  • Jeffers, J. R.
  • Yang, C. Y.
  • Nilsson, J. A.
  • Hall, M. A.
  • Rehg, J. E.
  • Yue, W.
  • Yu, J.
  • Zhang, L.
  • Onciu, M.
  • Sample, J. T.
  • Cleveland, John
  • Zambetti, G. P.

publication date

  • September 2008

journal

  • Molecular and Cellular Biology  Journal

abstract

  • The p53 tumor suppressor pathway limits oncogenesis by inducing cell cycle arrest or apoptosis. A key p53 target gene is PUMA, which encodes a BH3-only proapoptotic protein. Here we demonstrate that Puma deletion in the Emu-Myc mouse model of Burkitt lymphoma accelerates lymphomagenesis and that approximately 75% of Emu-Myc lymphomas naturally select against Puma protein expression. Furthermore, approximately 40% of primary human Burkitt lymphomas fail to express detectable levels of PUMA and in some tumors this is associated with DNA methylation. Burkitt lymphoma cell lines phenocopy the primary tumors with respect to DNA methylation and diminished PUMA expression, which can be reactivated following inhibition of DNA methyltransferases. These findings establish that PUMA is silenced in human malignancies, and they suggest PUMA as a target for the development of novel chemotherapeutics.

subject areas

  • Animals
  • Apoptosis
  • Apoptosis Regulatory Proteins
  • Azacitidine
  • B-Lymphocytes
  • Base Sequence
  • Burkitt Lymphoma
  • Cell Line, Tumor
  • Epigenesis, Genetic
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Histones
  • Humans
  • Methylation
  • Mice
  • Mice, Inbred C57BL
  • Molecular Sequence Data
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-2
  • Proto-Oncogene Proteins c-myc
  • Tumor Suppressor Protein p53
  • Tumor Suppressor Proteins
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Identity

PubMed Central ID

  • PMC2519737

International Standard Serial Number (ISSN)

  • 0270-7306

Digital Object Identifier (DOI)

  • 10.1128/mcb.00907-07

PubMed ID

  • 18573879
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Additional Document Info

start page

  • 5391

end page

  • 5402

volume

  • 28

issue

  • 17

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