Metastasis-associated protein 1 transgenic mice: a new model of spontaneous B-cell lymphomas.
Metastasis-associated protein 1 (MTA1), a component of the nuclear remodeling complex and the founding homologue of the MTA family, has been implicated in metastasis, but definitive causative evidence in an animal model system is currently lacking. Here, we show that MTA1 overexpression in transgenic mice is accompanied by a high incidence of spontaneous B cell lymphomas including diffuse large B cell lymphomas (DLBCL). Lymphocytes and lymphoma cells from MTA1-TG mice are hyperproliferative. Lymphomas were transplantable and of clonal origin and were characterized by down-regulation of p27Kip1 as well as up-regulation of Bcl2 and cyclin D1. The significance of these murine studies was established by evidence showing a widespread up-regulation of MTA1 in DLBCL from humans. These findings reveal a previously unrecognized role for the MTA1 pathway in the development of spontaneous B cell lymphomas, and offer a potential therapeutic target in B cell lymphomas. These observations suggest that MTA1-TG mice represent a new model of spontaneous DLBCL associated with high tumor incidence and could be used for therapeutic intervention studies.
Department of Molecular and Cellular Oncology, M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Rozita
R
Bagheri-Yarmand
Seetharaman
S
Balasenthil
Anupama E
AE
Gururaj
Amjad H
AH
Talukder
Yui-Hsi
YH
Wang
Ju Han
JH
Lee
Young Sik
YS
Kim
Xinaglan
X
Zhang
Daniel M
DM
Jones
L Jeffrey
LJ
Medeiros
L Clifton
LC
Stephens
Yong-Jun
YJ
Liu
Norman
N
Lee
Insun
I
Kim
Rakesh
R
Kumar
D000818:Animals; D015139:Blotting, Southern; D049109:Cell Proliferation; D004195:Disease Models, Animal; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000502:physiology*; D006655:Histone Deacetylases / Q000235:genetics; D006801:Humans; D008198:Lymph Nodes / Q000473:pathology; D016393:Lymphoma, B-Cell / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000209:etiology / Q000235:genetics* / Q000473:pathology; D008297:Male; D051379:Mice; D008819:Mice, Nude; D008822:Mice, Transgenic; D009362:Neoplasm Metastasis; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012097:Repressor Proteins / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015534:Trans-Activators; D014157:Transcription Factors / Q000235:genetics*; D014407:Tumor Cells, Cultured
C089320:MTA1 protein, human; C503336:Mta1 protein, mouse; D012333:RNA, Messenger; D012097:Repressor Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D006655:Histone Deacetylases