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.
Bagheri-Yarmand
Rozita
R
Department of Molecular and Cellular Oncology, M. D. Anderson Cancer Center, Houston, TX 77030, USA.
Balasenthil
Seetharaman
S
Gururaj
Anupama E
AE
Talukder
Amjad H
AH
Wang
Yui-Hsi
YH
Lee
Ju Han
JH
Kim
Young Sik
YS
Zhang
Xinaglan
X
Jones
Daniel M
DM
Medeiros
L Jeffrey
LJ
Stephens
L Clifton
LC
Liu
Yong-Jun
YJ
Lee
Norman
N
Kim
Insun
I
Kumar
Rakesh
R
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