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. 1994 Aug 1;13(15):3487–3495. doi: 10.1002/j.1460-2075.1994.tb06655.x

Cyclin D1/bcl-1 cooperates with myc genes in the generation of B-cell lymphoma in transgenic mice.

H Lovec 1, A Grzeschiczek 1, M B Kowalski 1, T Möröy 1
PMCID: PMC395252  PMID: 8062825

Abstract

The chromosomal translocation t(11:14) is associated with human lymphoid neoplasia affecting centrocytic B-cells of intermediate differentiation. As a consequence the cyclin D1 (bcl-1) gene is juxtaposed to the immunoglobulin heavy chain enhancer E mu. To show that transcriptional activation of cyclin D1 is causally involved in the generation of B-cell neoplasia we have generated transgenic mice that carry a cyclin D1 gene under the transcriptional control of the E mu element. E mu cyclin D1 transgenic mice show only very subtle alterations in the cycling behaviour of B-cell populations in the bone marrow compared with normal mice and do not develop lymphoid tumours. However, E mu-directed coexpression of cyclin D1 and N-MYC or L-MYC in double transgenic mice reveals a strong cooperative effect between MYC and cyclin D1 provoking the rapid development of clonal pre-B and B-cell lymphomas. Interestingly, crossing of cyclin D1 transgenic mice with E mu L-myc transgenics that express their transgene in both B- and T-cells but predominantly develop T-cell tumours leads in double transgenics exclusively to B-cell neoplasia. The data presented here demonstrate that transcriptional activation of cyclin D1 can oncogenically transform B-cells in concert with a myc gene. They establish cyclin D1 as a proto-oncogene whose activity appears to depend on a specific cell type as well as on a specific cooperating partner and link disturbances in the regulation of cell cycle progression to the development of human malignancies.

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Selected References

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