Cargando…

Fas Gene Mutation in the Progression of Adult T Cell Leukemia

Fas antigen (Apo-1/CD95) is an apoptosis-signaling cell surface receptor belonging to the tumor necrosis factor receptor superfamily. Adult T cell leukemia (ATL) cells express Fas antigen and show apoptosis after treatment with an anti-Fas monoclonal antibody. We established the ATL cell line KOB, w...

Descripción completa

Detalles Bibliográficos
Autores principales: Maeda, Takahiro, Yamada, Yasuaki, Moriuchi, Ryozou, Sugahara, Kazuyuki, Tsuruda, Kazuto, Joh, Tatsurou, Atogami, Sunao, Tsukasaki, Kunihiro, Tomonaga, Masao, Kamihira, Shimeru
Formato: Texto
Lenguaje:English
Publicado: The Rockefeller University Press 1999
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193006/
https://www.ncbi.nlm.nih.gov/pubmed/10190897
_version_ 1782147369058435072
author Maeda, Takahiro
Yamada, Yasuaki
Moriuchi, Ryozou
Sugahara, Kazuyuki
Tsuruda, Kazuto
Joh, Tatsurou
Atogami, Sunao
Tsukasaki, Kunihiro
Tomonaga, Masao
Kamihira, Shimeru
author_facet Maeda, Takahiro
Yamada, Yasuaki
Moriuchi, Ryozou
Sugahara, Kazuyuki
Tsuruda, Kazuto
Joh, Tatsurou
Atogami, Sunao
Tsukasaki, Kunihiro
Tomonaga, Masao
Kamihira, Shimeru
author_sort Maeda, Takahiro
collection PubMed
description Fas antigen (Apo-1/CD95) is an apoptosis-signaling cell surface receptor belonging to the tumor necrosis factor receptor superfamily. Adult T cell leukemia (ATL) cells express Fas antigen and show apoptosis after treatment with an anti-Fas monoclonal antibody. We established the ATL cell line KOB, which showed resistance to Fas-mediated apoptosis, and found that KOB expressed two forms of Fas mRNA, the normal form and a truncated form. The truncated transcript lacked 20 base pairs at exon 9, resulting in a frame shift and the generation of a premature stop codon at amino acid 239. The same mutation was detected in primary ascitic cells and peripheral blood cells. The mutation was not detected in lymph node cells, however, although all of the primary ATL cells were of the same clonal origin. A retroviral-mediated gene transfer of the truncated Fas to Jurkat cells rendered the cells resistant to Fas-mediated apoptosis, suggesting a dominant negative interference mechanism. These results indicate that an ATL subclone acquires a Fas mutation in the lymph nodes, enabling the subclone to escape from apoptosis mediated by the Fas/Fas ligand system and proliferate in the body. Mutation of the Fas gene may be one of the mechanisms underlying the progression of ATL.
format Text
id pubmed-2193006
institution National Center for Biotechnology Information
language English
publishDate 1999
publisher The Rockefeller University Press
record_format MEDLINE/PubMed
spelling pubmed-21930062008-04-16 Fas Gene Mutation in the Progression of Adult T Cell Leukemia Maeda, Takahiro Yamada, Yasuaki Moriuchi, Ryozou Sugahara, Kazuyuki Tsuruda, Kazuto Joh, Tatsurou Atogami, Sunao Tsukasaki, Kunihiro Tomonaga, Masao Kamihira, Shimeru J Exp Med Articles Fas antigen (Apo-1/CD95) is an apoptosis-signaling cell surface receptor belonging to the tumor necrosis factor receptor superfamily. Adult T cell leukemia (ATL) cells express Fas antigen and show apoptosis after treatment with an anti-Fas monoclonal antibody. We established the ATL cell line KOB, which showed resistance to Fas-mediated apoptosis, and found that KOB expressed two forms of Fas mRNA, the normal form and a truncated form. The truncated transcript lacked 20 base pairs at exon 9, resulting in a frame shift and the generation of a premature stop codon at amino acid 239. The same mutation was detected in primary ascitic cells and peripheral blood cells. The mutation was not detected in lymph node cells, however, although all of the primary ATL cells were of the same clonal origin. A retroviral-mediated gene transfer of the truncated Fas to Jurkat cells rendered the cells resistant to Fas-mediated apoptosis, suggesting a dominant negative interference mechanism. These results indicate that an ATL subclone acquires a Fas mutation in the lymph nodes, enabling the subclone to escape from apoptosis mediated by the Fas/Fas ligand system and proliferate in the body. Mutation of the Fas gene may be one of the mechanisms underlying the progression of ATL. The Rockefeller University Press 1999-04-05 /pmc/articles/PMC2193006/ /pubmed/10190897 Text en This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 Unported license, as described at http://creativecommons.org/licenses/by-nc-sa/4.0/).
spellingShingle Articles
Maeda, Takahiro
Yamada, Yasuaki
Moriuchi, Ryozou
Sugahara, Kazuyuki
Tsuruda, Kazuto
Joh, Tatsurou
Atogami, Sunao
Tsukasaki, Kunihiro
Tomonaga, Masao
Kamihira, Shimeru
Fas Gene Mutation in the Progression of Adult T Cell Leukemia
title Fas Gene Mutation in the Progression of Adult T Cell Leukemia
title_full Fas Gene Mutation in the Progression of Adult T Cell Leukemia
title_fullStr Fas Gene Mutation in the Progression of Adult T Cell Leukemia
title_full_unstemmed Fas Gene Mutation in the Progression of Adult T Cell Leukemia
title_short Fas Gene Mutation in the Progression of Adult T Cell Leukemia
title_sort fas gene mutation in the progression of adult t cell leukemia
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2193006/
https://www.ncbi.nlm.nih.gov/pubmed/10190897
work_keys_str_mv AT maedatakahiro fasgenemutationintheprogressionofadulttcellleukemia
AT yamadayasuaki fasgenemutationintheprogressionofadulttcellleukemia
AT moriuchiryozou fasgenemutationintheprogressionofadulttcellleukemia
AT sugaharakazuyuki fasgenemutationintheprogressionofadulttcellleukemia
AT tsurudakazuto fasgenemutationintheprogressionofadulttcellleukemia
AT johtatsurou fasgenemutationintheprogressionofadulttcellleukemia
AT atogamisunao fasgenemutationintheprogressionofadulttcellleukemia
AT tsukasakikunihiro fasgenemutationintheprogressionofadulttcellleukemia
AT tomonagamasao fasgenemutationintheprogressionofadulttcellleukemia
AT kamihirashimeru fasgenemutationintheprogressionofadulttcellleukemia