ARID3B induces malignant transformation of mouse embryonic fibroblasts and is strongly associated with malignant neuroblastoma.
ARID3B, a member of the AT-rich interaction domain (ARID) family of proteins, plays an essential role in the survival of neural crest during embryogenesis. Here, we report evidence that ARID3B is involved in the development of malignant neuroblastoma, a childhood tumor derived from neural crest. (a) ARID3B is expressed by all five cell lines derived from neuroblastoma tested by us. (b) Analysis of published DNA microarray data of fresh neuroblastoma tumors showed that ARID3B is expressed in 80% of stage IV tumors, whereas only in 9% of stage I-III+IVs tumors. (c) In vitro growth of several neuroblastoma cell lines is suppressed significantly by antisense as well as siRNA treatment. (d) An increase of the ARID3B expression level by transfection in the SY5Y neuroblastoma cell line enhances the malignancy in tumor growth assays in nu/nu mice. (e) ARID3B by itself can immortalize mouse embryonic fibroblasts (MEFs) in vitro and confers malignancy to MEF when transfected together with MYCN, the best characterized oncogene for neuroblastoma. Thus, ARID3B seems to play a key role in the malignant transformation of neuroblastoma and may serve not only as a marker of malignancy but also as a potential target for cancer therapy of stage IV neuroblastoma for which there is currently no effective treatment available.
Kobayashi
Kenichiro
K
Laboratory for Stem Cell Biology, RIKEN Center for Development Biology, Graduate School of Medicine, Kobe University, Kobe, Hyogo, Japan.
Era
Takumi
T
Takebe
Atsushi
A
Jakt
Lars Martin
LM
Nishikawa
Shin-Ichi
S
D000818:Animals; D002471:Cell Transformation, Neoplastic; D004268:DNA-Binding Proteins / Q000235:genetics*; D005347:Fibroblasts / Q000473:pathology* / Q000502:physiology*; D015972:Gene Expression Regulation, Neoplastic; D051379:Mice; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology*; D020411:Oligonucleotide Array Sequence Analysis; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering / Q000235:genetics
C510769:Arid3b protein, mouse; D004268:DNA-Binding Proteins; D016376:Oligonucleotides, Antisense; D034741:RNA, Small Interfering