MAL gene expression in esophageal cancer suppresses motility, invasion and tumorigenicity and enhances apoptosis through the Fas pathway

Koshi Mimori, Takeshi Shiraishi, Kohjiro Mashino, Hideto Sonoda, Keishi Yamashita, Keiji Yoshinaga, Takaaki Masuda, Tohru Utsunomiya, Miguel A. Alonso, Hiroshi Inoue, Masaki Mori

研究成果: ジャーナルへの寄稿記事

55 引用 (Scopus)

抄録

We isolated the MAL (T-lymphocyte maturation associated protein) gene from differentially expressed products of esophageal epithelium relative to esophageal carcinoma tissues. The Mal protein has been demonstrated as being a component of the protein machinery for apical transport in epithelial polarized cells. In this study, we describe the reduced expression of MAL in all 39 cases of esophageal carcinoma tested and 60 other human carcinomas. MAL gene transcription was induced in three out of 13 esophageal carcinoma cell lines by treatment with the demethylating agent 5-aza-2′-deoxycytidine (DAC), and in nine additional cell lines by simultaneous treatment with trichostatin A, an inhibitor of deacetylation, and DAC. We established a stable MAL gene transfectant whose expression was regulated by subcutaneous doxycycline injection in nude mice. Tumor growth was suppressed in cells expressing TE3-MAL compared with TE3 parent cells or cells not expressing TE3-MAL with doxycycline injection (20 μg/body) (P < 0.01). Additionally, the TE3-MAL transfectant cells exhibited decreased cellular motility, a G1/S transition block and increased levels of apoptosis, concomitant with increased expression of Fas receptor in vitro. The apoptotic staining in MAL-expressing tumors was confirmed by TUNEL assay. Therefore, we conclude that expression of MAL was frequently decreased or diminished in gastrointestinal tract cancers, and that Mal expression confers reduced tumorigenicity in vivo to tumor TE3 cells through the induction of apoptosis via the Fas signaling pathway.

元の言語英語
ページ(範囲)3463-3471
ページ数9
ジャーナルOncogene
22
発行部数22
DOI
出版物ステータス出版済み - 5 29 2003

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Esophageal Neoplasms
Apoptosis
Gene Expression
Carcinoma
Doxycycline
decitabine
Myelin and Lymphocyte-Associated Proteolipid Proteins
trichostatin A
Genes
CD95 Antigens
Cell Line
Neoplasms
Gastrointestinal Neoplasms
In Situ Nick-End Labeling
Subcutaneous Injections
Nude Mice
Proteins
Epithelium
Epithelial Cells
Staining and Labeling

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Cancer Research

これを引用

MAL gene expression in esophageal cancer suppresses motility, invasion and tumorigenicity and enhances apoptosis through the Fas pathway. / Mimori, Koshi; Shiraishi, Takeshi; Mashino, Kohjiro; Sonoda, Hideto; Yamashita, Keishi; Yoshinaga, Keiji; Masuda, Takaaki; Utsunomiya, Tohru; Alonso, Miguel A.; Inoue, Hiroshi; Mori, Masaki.

:: Oncogene, 巻 22, 番号 22, 29.05.2003, p. 3463-3471.

研究成果: ジャーナルへの寄稿記事

Mimori, K, Shiraishi, T, Mashino, K, Sonoda, H, Yamashita, K, Yoshinaga, K, Masuda, T, Utsunomiya, T, Alonso, MA, Inoue, H & Mori, M 2003, 'MAL gene expression in esophageal cancer suppresses motility, invasion and tumorigenicity and enhances apoptosis through the Fas pathway', Oncogene, 巻. 22, 番号 22, pp. 3463-3471. https://doi.org/10.1038/sj.onc.1206378
Mimori, Koshi ; Shiraishi, Takeshi ; Mashino, Kohjiro ; Sonoda, Hideto ; Yamashita, Keishi ; Yoshinaga, Keiji ; Masuda, Takaaki ; Utsunomiya, Tohru ; Alonso, Miguel A. ; Inoue, Hiroshi ; Mori, Masaki. / MAL gene expression in esophageal cancer suppresses motility, invasion and tumorigenicity and enhances apoptosis through the Fas pathway. :: Oncogene. 2003 ; 巻 22, 番号 22. pp. 3463-3471.
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abstract = "We isolated the MAL (T-lymphocyte maturation associated protein) gene from differentially expressed products of esophageal epithelium relative to esophageal carcinoma tissues. The Mal protein has been demonstrated as being a component of the protein machinery for apical transport in epithelial polarized cells. In this study, we describe the reduced expression of MAL in all 39 cases of esophageal carcinoma tested and 60 other human carcinomas. MAL gene transcription was induced in three out of 13 esophageal carcinoma cell lines by treatment with the demethylating agent 5-aza-2′-deoxycytidine (DAC), and in nine additional cell lines by simultaneous treatment with trichostatin A, an inhibitor of deacetylation, and DAC. We established a stable MAL gene transfectant whose expression was regulated by subcutaneous doxycycline injection in nude mice. Tumor growth was suppressed in cells expressing TE3-MAL compared with TE3 parent cells or cells not expressing TE3-MAL with doxycycline injection (20 μg/body) (P < 0.01). Additionally, the TE3-MAL transfectant cells exhibited decreased cellular motility, a G1/S transition block and increased levels of apoptosis, concomitant with increased expression of Fas receptor in vitro. The apoptotic staining in MAL-expressing tumors was confirmed by TUNEL assay. Therefore, we conclude that expression of MAL was frequently decreased or diminished in gastrointestinal tract cancers, and that Mal expression confers reduced tumorigenicity in vivo to tumor TE3 cells through the induction of apoptosis via the Fas signaling pathway.",
author = "Koshi Mimori and Takeshi Shiraishi and Kohjiro Mashino and Hideto Sonoda and Keishi Yamashita and Keiji Yoshinaga and Takaaki Masuda and Tohru Utsunomiya and Alonso, {Miguel A.} and Hiroshi Inoue and Masaki Mori",
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T1 - MAL gene expression in esophageal cancer suppresses motility, invasion and tumorigenicity and enhances apoptosis through the Fas pathway

AU - Mimori, Koshi

AU - Shiraishi, Takeshi

AU - Mashino, Kohjiro

AU - Sonoda, Hideto

AU - Yamashita, Keishi

AU - Yoshinaga, Keiji

AU - Masuda, Takaaki

AU - Utsunomiya, Tohru

AU - Alonso, Miguel A.

AU - Inoue, Hiroshi

AU - Mori, Masaki

PY - 2003/5/29

Y1 - 2003/5/29

N2 - We isolated the MAL (T-lymphocyte maturation associated protein) gene from differentially expressed products of esophageal epithelium relative to esophageal carcinoma tissues. The Mal protein has been demonstrated as being a component of the protein machinery for apical transport in epithelial polarized cells. In this study, we describe the reduced expression of MAL in all 39 cases of esophageal carcinoma tested and 60 other human carcinomas. MAL gene transcription was induced in three out of 13 esophageal carcinoma cell lines by treatment with the demethylating agent 5-aza-2′-deoxycytidine (DAC), and in nine additional cell lines by simultaneous treatment with trichostatin A, an inhibitor of deacetylation, and DAC. We established a stable MAL gene transfectant whose expression was regulated by subcutaneous doxycycline injection in nude mice. Tumor growth was suppressed in cells expressing TE3-MAL compared with TE3 parent cells or cells not expressing TE3-MAL with doxycycline injection (20 μg/body) (P < 0.01). Additionally, the TE3-MAL transfectant cells exhibited decreased cellular motility, a G1/S transition block and increased levels of apoptosis, concomitant with increased expression of Fas receptor in vitro. The apoptotic staining in MAL-expressing tumors was confirmed by TUNEL assay. Therefore, we conclude that expression of MAL was frequently decreased or diminished in gastrointestinal tract cancers, and that Mal expression confers reduced tumorigenicity in vivo to tumor TE3 cells through the induction of apoptosis via the Fas signaling pathway.

AB - We isolated the MAL (T-lymphocyte maturation associated protein) gene from differentially expressed products of esophageal epithelium relative to esophageal carcinoma tissues. The Mal protein has been demonstrated as being a component of the protein machinery for apical transport in epithelial polarized cells. In this study, we describe the reduced expression of MAL in all 39 cases of esophageal carcinoma tested and 60 other human carcinomas. MAL gene transcription was induced in three out of 13 esophageal carcinoma cell lines by treatment with the demethylating agent 5-aza-2′-deoxycytidine (DAC), and in nine additional cell lines by simultaneous treatment with trichostatin A, an inhibitor of deacetylation, and DAC. We established a stable MAL gene transfectant whose expression was regulated by subcutaneous doxycycline injection in nude mice. Tumor growth was suppressed in cells expressing TE3-MAL compared with TE3 parent cells or cells not expressing TE3-MAL with doxycycline injection (20 μg/body) (P < 0.01). Additionally, the TE3-MAL transfectant cells exhibited decreased cellular motility, a G1/S transition block and increased levels of apoptosis, concomitant with increased expression of Fas receptor in vitro. The apoptotic staining in MAL-expressing tumors was confirmed by TUNEL assay. Therefore, we conclude that expression of MAL was frequently decreased or diminished in gastrointestinal tract cancers, and that Mal expression confers reduced tumorigenicity in vivo to tumor TE3 cells through the induction of apoptosis via the Fas signaling pathway.

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