LMO3 interacts with neuronal transcription factor, HEN2, and acts as an oncogene in neuroblastoma.
LIM-only proteins (LMO), which consist of LMO1, LMO2, LMO3, and LMO4, are involved in cell fate determination and differentiation during embryonic development. Accumulating evidence suggests that LMO1 and LMO2 act as oncogenic proteins in T-cell acute lymphoblastic leukemia, whereas LMO4 has recently been implicated in the genesis of breast cancer. However, little is known about the role of LMO3 in either tumorigenesis or development. In the present study, we have identified LMO3 and HEN2, which encodes a neuronal basic helix-loop-helix protein, as genes whose expression levels were higher in unfavorable neuroblastomas compared with those of favorable tumors. Immunoprecipitation and immunostaining experiments showed that LMO3 was associated with HEN2 in mammalian cell nucleus. Human neuroblastoma SH-SY5Y cells stably overexpressing LMO3 showed a marked increase in cell growth, a promotion of colony formation in soft agar medium, and a rapid tumor growth in nude mice compared with the control transfectants. More importantly, the increased expression of LMO3 and HEN2 was significantly associated with a poor prognosis in 87 primary neuroblastomas. These results suggest that the deregulated expression of neuronal-specific LMO3 and HEN2 contributes to the genesis and progression of human neuroblastoma in a lineage-specific manner.
Aoyama
Mineyoshi
M
Division of Biochemistry, Chiba Cancer Center Research Institute, Japan.
Ozaki
Toshinori
T
Inuzuka
Hiroyuki
H
Tomotsune
Daihachiro
D
Hirato
Junko
J
Okamoto
Yoshiaki
Y
Tokita
Hisashi
H
Ohira
Miki
M
Nakagawara
Akira
A
D048868:Adaptor Proteins, Signal Transducing; D000595:Amino Acid Sequence; D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins; D048708:Cell Growth Processes / Q000235:genetics; D045744:Cell Line, Tumor; D002675:Child, Preschool; D004268:DNA-Binding Proteins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006801:Humans; D007223:Infant; D060588:LIM Domain Proteins; D051379:Mice; D008819:Mice, Nude; D008969:Molecular Sequence Data; D009447:Neuroblastoma / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015513:Oncogene Proteins / Q000235:genetics* / Q000378:metabolism; D009857:Oncogenes / Q000502:physiology; D014162:Transfection
D048868:Adaptor Proteins, Signal Transducing; D051792:Basic Helix-Loop-Helix Proteins; D004268:DNA-Binding Proteins; D060588:LIM Domain Proteins; D015513:Oncogene Proteins; C502335:LMO3 protein, human; C076747:NHLH2 protein, human