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
Ito E, Honma R, Imai J, Azuma S, Kanno T, Mori S, Yoshie O, Nisho J, Iwasaki H, Yoshida K, Gohda J, Inoue J, Watanabe S and Semba K
Am J Pathol
Cancer Research/Cell Biology
Cells of the human osteosarcoma cell line U2OS were nucleofected with a plasmid encoding the above mentioned splicing variant of the chimeric transcription factor. They showed a significant induction of TALLA-1.
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.
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