A tetraspanin-family protein, T-cell acute lymphoblastic leukemia-associated antigen 1, is induced by the Ewing's sarcoma-Wilms' tumor 1 fusion protein of desmoplastic small round-cell tumor.
Recurrent chromosomal translocations in neoplasms often generate hybrid genes that play critical roles in tumorigenesis. Desmoplastic small round-cell tumor (DSRCT) is an aggressive malignancy associated with the chromosomal translocation t(11;22)(p13;q12). This translocation generates a chimeric transcription factor, EWS-WT1, which consists of the transcriptional activation domain of the Ewing's sarcoma (EWS) protein and the DNA binding domain of the Wilms' tumor 1 (WT1) protein. One of the splice variants, EWS-WT1(-KTS) lacks three amino acid residues (Lys-Thr-Ser) in the DNA binding domain and transforms NIH3T3 cells. Therefore, it is likely that aberrant gene expression caused by EWS-WT1(-KTS) is involved in the malignant phenotype of DSRCT. Microarray analysis of 9600 human genes revealed that a gene encoding a tetraspanin-family protein, T-cell acute lymphoblastic leukemia-associated antigen 1 (TALLA-1), was induced in EWS-WT1(-KTS)-expressing cell clones. This induction was EWS-WT1(-KTS)-specific, and more importantly, TALLA-1 protein was expressed in the three independent cases of DSRCT. Tetraspanin-family genes encode transmembrane proteins that regulate various cell processes such as cell adhesion, migration and metastasis. Our findings provide a novel insight into the malignant phenotype of DSRCT, suggesting that TALLA-1 is a useful marker for diagnosis and a potential target for the therapy of DSRCT.
Ito
Emi
E
Division of Cancer Genomics, Department of Cancer Biology, The Institute of Medical Science, The University of Tokyo, Tokyo.
Honma
Reiko
R
Imai
Jun-ichi
J
Azuma
Sakura
S
Kanno
Takayuki
T
Mori
Shigeo
S
Yoshie
Osamu
O
Nishio
Jun
J
Iwasaki
Hiroshi
H
Yoshida
Koichi
K
Gohda
Jin
J
Inoue
Jun-Ichiro
J
Watanabe
Shinya
S
Semba
Kentaro
K
D018288:Carcinoma, Small Cell / Q000378:metabolism*; D045744:Cell Line, Tumor; D020869:Gene Expression Profiling; D006801:Humans; D008562:Membrane Glycoproteins / Q000235:genetics / Q000378:metabolism*; D020411:Oligonucleotide Array Sequence Analysis; D015514:Oncogene Proteins, Fusion / Q000235:genetics / Q000378:metabolism*; D010534:Peritoneal Neoplasms / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D014162:Transfection
C106032:EWS1-WT1 fusion protein, human; D008562:Membrane Glycoproteins; D015514:Oncogene Proteins, Fusion; D012333:RNA, Messenger; C028388:thymus-leukemia antigens