Upregulation of the oncogenic helix-loop-helix protein Id2 in Ewing sarcoma.
OBJECTIVE
Id helix-loop-helix proteins function as regulators of cell growth and differentiation. However, they can induce malignant transformation when overexpressed. The EWS/ETS chimeric proteins in Ewing sarcoma act as aberrant transcription factors leading to tumorigenic processes. An enhanced expression of the Id2 gene in Ewing sarcoma cells was previously shown by gene array techniques. We investigated the expression of Id2 at the protein and gene level in Ewing sarcoma.


METHODS
We evaluated the expression of Id2 protein using immunohistochemistry in formalin-fixed, paraffin-embedded specimens from a total of 71 cases of Ewing sarcoma. Additionally, a Ewing sarcoma cell line was examined by real-time quantitative PCR.


RESULTS
Id2 expression was observed in 65 cases (91.5%) of the 71 total cases examined and a high level of Id2 expression was observed in 45 of these cases (63.8%). In tumor cells, Id2 proteins displayed cytoplasmic as well as nuclear localization. The amplification of the Id2 gene was not noted in a Ewing sarcoma cell line using real-time quantitative PCR. The crossing points of Id2 in the Ewing sarcoma cell line, control fibroblast, and osteosarcoma cell line were 18.54 +/- 0.16, 18.25, and 18.34, respectively.


CONCLUSIONS
Our data support a role for increased Id2 protein expression in Ewing sarcoma. However, this overexpression of the Id2 protein could not be confirmed by a corresponding change at the gene level in a Ewing sarcoma cell line.
Park
Hye-Rim
HR
Department of Pathology, College of Medicine, Hallym University, Anyang, Korea.
Jung
Woon Won
WW
Kim
Hyun Sook
HS
Santini-Araujo
Eduard
E
Kalil
Ricardo K
RK
Bacchini
Patrizia
P
Bertoni
Franco
F
Unni
K Krishnan
KK
Park
Yong-Koo
YK
D014408:Biomarkers, Tumor / Q000032:analysis*; D001859:Bone Neoplasms / Q000737:chemistry*; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D051797:Inhibitor of Differentiation Protein 2 / Q000032:analysis*; D016133:Polymerase Chain Reaction; D012189:Retrospective Studies; D012512:Sarcoma, Ewing / Q000737:chemistry*; D015854:Up-Regulation
D014408:Biomarkers, Tumor; C497450:ID2 protein, human; D051797:Inhibitor of Differentiation Protein 2