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

Emi Ito, Reiko Honma, Jun Ichi Imai, Sakura Azuma, Takayuki Kanno, Shigeo Mori, Osamu Yoshie, Jun Nishio, Hiroshi Iwasaki, Koichi Yoshida, Jin Gohda, Jun Ichiro Inoue, Shinya Watanabe, Kentaro Senba

Research output: Contribution to journalArticle

36 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)2165-2172
Number of pages8
JournalAmerican Journal of Pathology
Volume163
Issue number6
Publication statusPublished - 2003 Dec
Externally publishedYes

Fingerprint

Desmoplastic Small Round Cell Tumor
Precursor T-Cell Lymphoblastic Leukemia-Lymphoma
Ewing's Sarcoma
Wilms Tumor
Antigens
Genetic Translocation
Proteins
Genes
Phenotype
DNA-Binding Proteins
Microarray Analysis
Cell Adhesion
Transcriptional Activation
Cell Movement
Neoplasms
Carcinogenesis
Transcription Factors
Clone Cells
Neoplasm Metastasis
Gene Expression

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Cite this

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, Emi; Honma, Reiko; Imai, Jun Ichi; Azuma, Sakura; Kanno, Takayuki; Mori, Shigeo; Yoshie, Osamu; Nishio, Jun; Iwasaki, Hiroshi; Yoshida, Koichi; Gohda, Jin; Inoue, Jun Ichiro; Watanabe, Shinya; Senba, Kentaro.

In: American Journal of Pathology, Vol. 163, No. 6, 12.2003, p. 2165-2172.

Research output: Contribution to journalArticle

Ito, E, Honma, R, Imai, JI, Azuma, S, Kanno, T, Mori, S, Yoshie, O, Nishio, J, Iwasaki, H, Yoshida, K, Gohda, J, Inoue, JI, Watanabe, S & Senba, K 2003, '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', American Journal of Pathology, vol. 163, no. 6, pp. 2165-2172.
Ito, Emi ; Honma, Reiko ; Imai, Jun Ichi ; Azuma, Sakura ; Kanno, Takayuki ; Mori, Shigeo ; Yoshie, Osamu ; Nishio, Jun ; Iwasaki, Hiroshi ; Yoshida, Koichi ; Gohda, Jin ; Inoue, Jun Ichiro ; Watanabe, Shinya ; Senba, Kentaro. / 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. In: American Journal of Pathology. 2003 ; Vol. 163, No. 6. pp. 2165-2172.
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abstract = "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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AU - Ito, Emi

AU - Honma, Reiko

AU - Imai, Jun Ichi

AU - Azuma, Sakura

AU - Kanno, Takayuki

AU - Mori, Shigeo

AU - Yoshie, Osamu

AU - Nishio, Jun

AU - Iwasaki, Hiroshi

AU - Yoshida, Koichi

AU - Gohda, Jin

AU - Inoue, Jun Ichiro

AU - Watanabe, Shinya

AU - Senba, Kentaro

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N2 - 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.

AB - 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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