Overexpression of c-Maf contributes to T-cell lymphoma in both mice and human.
c-Maf translocation or overexpression has been observed in human multiple myeloma. Although c-maf might function as an oncogene in multiple myeloma, a role for this gene in other cancers has not been shown. In this study, we have found that mice transgenic for c-Maf whose expression was direct to the T-cell compartment developed T-cell lymphoma. Moreover, we showed that cyclin D2, integrin beta(7), and ARK5 were up-regulated in c-Maf transgenic lymphoma cells. Furthermore, 60% of human T-cell lymphomas (11 of 18 cases), classified as angioimmunoblastic T-cell lymphoma, were found to express c-Maf. These results suggest that c-Maf might cause a type of T-cell lymphoma in both mice and humans and that ARK5, in addition to cyclin D2 and integrin beta(7), might be downstream target genes of c-Maf leading to malignant transformation.
Morito
Naoki
N
Department of Anatomy and Embryology, Biomolecular and Integrated Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8575, Japan.
Yoh
Keigyou
K
Fujioka
Yuki
Y
Nakano
Takako
T
Shimohata
Homare
H
Hashimoto
Yuko
Y
Yamada
Akiko
A
Maeda
Atsuko
A
Matsuno
Fumihiko
F
Hata
Hiroyuki
H
Suzuki
Atsushi
A
Imagawa
Shigehiko
S
Mitsuya
Hiroaki
H
Esumi
Hiroyasu
H
Koyama
Akio
A
Yamamoto
Masayuki
M
Mori
Naoyoshi
N
Takahashi
Satoru
S
D000818:Animals; D002471:Cell Transformation, Neoplastic; D056742:Cyclin D2; D016213:Cyclins / Q000096:biosynthesis; D020869:Gene Expression Profiling; D006801:Humans; D039641:Integrin beta Chains / Q000096:biosynthesis; D016399:Lymphoma, T-Cell / Q000235:genetics* / Q000503:physiopathology; D051379:Mice; D011494:Protein Kinases / Q000096:biosynthesis; D051257:Proto-Oncogene Proteins c-maf / Q000096:biosynthesis* / Q000502:physiology; D012097:Repressor Proteins / Q000096:biosynthesis; D015854:Up-Regulation
C080336:CCND2 protein, human; C486196:Ccnd2 protein, mouse; D056742:Cyclin D2; D016213:Cyclins; D039641:Integrin beta Chains; C495607:MAF protein, human; C495608:Maf protein, mouse; D051257:Proto-Oncogene Proteins c-maf; D012097:Repressor Proteins; C091368:integrin beta7; D011494:Protein Kinases; C470845:NUAK1 protein, human