TY - JOUR
T1 - Metastasis-associated protein 1 transgenic mice
T2 - A new model of spontaneous B-cell lymphomas
AU - Bagheri-Yarmand, Rozita
AU - Balasenthil, Seetharaman
AU - Gururaj, Anupama E.
AU - Talukder, Amjad H.
AU - Wang, Yui Hsi
AU - Ju, Han Lee
AU - Young, Sik Kim
AU - Zhang, Xinaglan
AU - Jones, Daniel M.
AU - Medeiros, L. Jeffrey
AU - Stephens, L. Clifton
AU - Liu, Yong Jun
AU - Lee, Norman
AU - Kim, Insun
AU - Kumar, Rakesh
PY - 2007/8/1
Y1 - 2007/8/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=34547634904&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=34547634904&partnerID=8YFLogxK
U2 - 10.1158/0008-5472.CAN-07-0748
DO - 10.1158/0008-5472.CAN-07-0748
M3 - Article
C2 - 17671172
AN - SCOPUS:34547634904
SN - 0008-5472
VL - 67
SP - 7062
EP - 7067
JO - Cancer Research
JF - Cancer Research
IS - 15
ER -