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The human BCL6 transgene promotes the development of lymphomas in the mouse.

BCL6, a gene on chromosome 3, band q27, encodes a zinc finger transcriptional repressor that is needed for germinal center formation and has been implicated in the pathogenesis of some human lymphomas when it is mutated or involved in chromosomal rearrangements. To explore further the mechanisms of action of BCL6 in lymphomagenesis, we developed a transgenic mouse model mimicking a common translocation, the t(3, 14)(q27;q32), in human lymphomas. The transgenic mice develop normally and express the transgenic BCL6 protein constitutively in lymphocytes. A small fraction of the animals develop B and T cell lymphomas after a long latency period, but the incidence is dramatically enhanced following administration of N-ethyl-N-nitrosourea, a carcinogen that induces DNA mutations. The N-ethyl-N-nitrosourea-induced lymphomas spread widely, were exclusively T cell, expressed the BCL6 protein, and occurred only in the transgenic mice. Because BCL6 expression has been reported in a number of T cell tumors as well as in the more commonly occurring B cell lymphomas in humans, our transgenic mice provide a model for the study of human lymphomas.

Pubmed ID: 15375218

Authors

  • Baron BW
  • Anastasi J
  • Montag A
  • Huo D
  • Baron RM
  • Karrison T
  • Thirman MJ
  • Subudhi SK
  • Chin RK
  • Felsher DW
  • Fu YX
  • McKeithan TW
  • Baron JM

Journal

Proceedings of the National Academy of Sciences of the United States of America

Publication Data

September 28, 2004

Associated Grants

  • Agency: NCI NIH HHS, Id: CA63365
  • Agency: NCI NIH HHS, Id: P30 CA144599

Mesh Terms

  • Animals
  • Animals, Newborn
  • DNA-Binding Proteins
  • Ethylnitrosourea
  • Female
  • Gene Expression
  • Humans
  • Immunohistochemistry
  • Lymphoma, T-Cell
  • Male
  • Mice
  • Mice, Transgenic
  • Oncogenes
  • Proto-Oncogene Proteins
  • Proto-Oncogene Proteins c-bcl-6
  • RNA, Messenger
  • Reverse Transcriptase Polymerase Chain Reaction
  • Transcription Factors
  • Zinc Fingers