Expression of constitutively nuclear cyclin D1 in murine lymphocytes induces B-cell lymphoma.

Abstract:

:Mantle cell lymphoma (MCL) is a B-cell lymphoma characterized by overexpression of cyclin D1 due to the t(11;14) chromosomal translocation. While expression of cyclin D1 correlates with MCL development, expression of wild-type (WT) cyclin D1 transgene in murine lymphocytes is unable to drive B-cell lymphoma. As cyclin D1 mutants that are refractory to nuclear export display heighten oncogenicity in vitro compared with WT D1, we generated mice expressing FLAG-D1/T286A, a constitutively nuclear mutant, under the control of the immunoglobulin enhancer, Emu. D1/T286A transgenic mice universally develop a mature B-cell lymphoma. Expression of D1/T286A in B lymphocytes results in S phase entry in resting lymphocytes and increased apoptosis in spleens of young premalignant mice. Lymphoma onset correlates with perturbations in p53/MDM2/p19Arf expression and with BcL-2 overexpression suggesting that alterations in one or both of these pathways may contribute to lymphoma development. Our results describe a cyclin D1-driven model of B-cell lymphomagenesis and provide evidence that nuclear-retention of cyclin D1 is oncogenic in vivo.

journal_name

Oncogene

journal_title

Oncogene

authors

Gladden AB,Woolery R,Aggarwal P,Wasik MA,Diehl JA

doi

10.1038/sj.onc.1209147

subject

Has Abstract

pub_date

2006-02-16 00:00:00

pages

998-1007

issue

7

eissn

0950-9232

issn

1476-5594

pii

1209147

journal_volume

25

pub_type

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