Cargando…

Xenotransplantation elicits salient tumorigenicity of adult T‐cell leukemia‐derived cells via aberrant AKT activation

The transplantation of human cancer cells into immunodeficient NOD/SCID/IL‐2Rγc(null) (NOG) mice often causes highly malignant cell populations like cancer stem cells to emerge. Here, by serial transplantation in NOG mice, we established two highly tumorigenic adult T‐cell leukemia‐derived cell line...

Descripción completa

Detalles Bibliográficos
Autores principales: Yamaguchi, Kazunori, Takanashi, Tomoka, Nasu, Kentaro, Tamai, Keiichi, Mochizuki, Mai, Satoh, Ikuro, Ine, Shoji, Sasaki, Osamu, Satoh, Kennichi, Tanaka, Nobuyuki, Harigae, Hideo, Sugamura, Kazuo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970830/
https://www.ncbi.nlm.nih.gov/pubmed/26928911
http://dx.doi.org/10.1111/cas.12921
_version_ 1782446020339171328
author Yamaguchi, Kazunori
Takanashi, Tomoka
Nasu, Kentaro
Tamai, Keiichi
Mochizuki, Mai
Satoh, Ikuro
Ine, Shoji
Sasaki, Osamu
Satoh, Kennichi
Tanaka, Nobuyuki
Harigae, Hideo
Sugamura, Kazuo
author_facet Yamaguchi, Kazunori
Takanashi, Tomoka
Nasu, Kentaro
Tamai, Keiichi
Mochizuki, Mai
Satoh, Ikuro
Ine, Shoji
Sasaki, Osamu
Satoh, Kennichi
Tanaka, Nobuyuki
Harigae, Hideo
Sugamura, Kazuo
author_sort Yamaguchi, Kazunori
collection PubMed
description The transplantation of human cancer cells into immunodeficient NOD/SCID/IL‐2Rγc(null) (NOG) mice often causes highly malignant cell populations like cancer stem cells to emerge. Here, by serial transplantation in NOG mice, we established two highly tumorigenic adult T‐cell leukemia‐derived cell lines, ST1‐N6 and TL‐Om1‐N8. When transplanted s.c., these cells formed tumors significantly earlier and from fewer initial cells than their parental lines ST1 and TL‐Om1. We found that protein kinase B (AKT) signaling was upregulated in ST1‐N6 and TL‐Om1‐N8 cells, and that this upregulation was due to the decreased expression of a negative regulator, INPP5D. Furthermore, the introduction of a constitutively active AKT mutant expression vector into ST1 cells augmented the tumorigenicity of the cells, whereas treatment with the AKT inhibitor MK‐2206 attenuated the progression of tumors induced by ST1‐N6 cells. Collectively, our results reveal that the AKT signaling pathway plays a critical role in the malignancy of adult T‐cell leukemia‐derived cells.
format Online
Article
Text
id pubmed-4970830
institution National Center for Biotechnology Information
language English
publishDate 2016
publisher John Wiley and Sons Inc.
record_format MEDLINE/PubMed
spelling pubmed-49708302016-08-11 Xenotransplantation elicits salient tumorigenicity of adult T‐cell leukemia‐derived cells via aberrant AKT activation Yamaguchi, Kazunori Takanashi, Tomoka Nasu, Kentaro Tamai, Keiichi Mochizuki, Mai Satoh, Ikuro Ine, Shoji Sasaki, Osamu Satoh, Kennichi Tanaka, Nobuyuki Harigae, Hideo Sugamura, Kazuo Cancer Sci Original Articles The transplantation of human cancer cells into immunodeficient NOD/SCID/IL‐2Rγc(null) (NOG) mice often causes highly malignant cell populations like cancer stem cells to emerge. Here, by serial transplantation in NOG mice, we established two highly tumorigenic adult T‐cell leukemia‐derived cell lines, ST1‐N6 and TL‐Om1‐N8. When transplanted s.c., these cells formed tumors significantly earlier and from fewer initial cells than their parental lines ST1 and TL‐Om1. We found that protein kinase B (AKT) signaling was upregulated in ST1‐N6 and TL‐Om1‐N8 cells, and that this upregulation was due to the decreased expression of a negative regulator, INPP5D. Furthermore, the introduction of a constitutively active AKT mutant expression vector into ST1 cells augmented the tumorigenicity of the cells, whereas treatment with the AKT inhibitor MK‐2206 attenuated the progression of tumors induced by ST1‐N6 cells. Collectively, our results reveal that the AKT signaling pathway plays a critical role in the malignancy of adult T‐cell leukemia‐derived cells. John Wiley and Sons Inc. 2016-04-07 2016-05 /pmc/articles/PMC4970830/ /pubmed/26928911 http://dx.doi.org/10.1111/cas.12921 Text en © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association. This is an open access article under the terms of the Creative Commons Attribution‐NonCommercial‐NoDerivs (http://creativecommons.org/licenses/by-nc-nd/4.0/) License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non‐commercial and no modifications or adaptations are made.
spellingShingle Original Articles
Yamaguchi, Kazunori
Takanashi, Tomoka
Nasu, Kentaro
Tamai, Keiichi
Mochizuki, Mai
Satoh, Ikuro
Ine, Shoji
Sasaki, Osamu
Satoh, Kennichi
Tanaka, Nobuyuki
Harigae, Hideo
Sugamura, Kazuo
Xenotransplantation elicits salient tumorigenicity of adult T‐cell leukemia‐derived cells via aberrant AKT activation
title Xenotransplantation elicits salient tumorigenicity of adult T‐cell leukemia‐derived cells via aberrant AKT activation
title_full Xenotransplantation elicits salient tumorigenicity of adult T‐cell leukemia‐derived cells via aberrant AKT activation
title_fullStr Xenotransplantation elicits salient tumorigenicity of adult T‐cell leukemia‐derived cells via aberrant AKT activation
title_full_unstemmed Xenotransplantation elicits salient tumorigenicity of adult T‐cell leukemia‐derived cells via aberrant AKT activation
title_short Xenotransplantation elicits salient tumorigenicity of adult T‐cell leukemia‐derived cells via aberrant AKT activation
title_sort xenotransplantation elicits salient tumorigenicity of adult t‐cell leukemia‐derived cells via aberrant akt activation
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4970830/
https://www.ncbi.nlm.nih.gov/pubmed/26928911
http://dx.doi.org/10.1111/cas.12921
work_keys_str_mv AT yamaguchikazunori xenotransplantationelicitssalienttumorigenicityofadulttcellleukemiaderivedcellsviaaberrantaktactivation
AT takanashitomoka xenotransplantationelicitssalienttumorigenicityofadulttcellleukemiaderivedcellsviaaberrantaktactivation
AT nasukentaro xenotransplantationelicitssalienttumorigenicityofadulttcellleukemiaderivedcellsviaaberrantaktactivation
AT tamaikeiichi xenotransplantationelicitssalienttumorigenicityofadulttcellleukemiaderivedcellsviaaberrantaktactivation
AT mochizukimai xenotransplantationelicitssalienttumorigenicityofadulttcellleukemiaderivedcellsviaaberrantaktactivation
AT satohikuro xenotransplantationelicitssalienttumorigenicityofadulttcellleukemiaderivedcellsviaaberrantaktactivation
AT ineshoji xenotransplantationelicitssalienttumorigenicityofadulttcellleukemiaderivedcellsviaaberrantaktactivation
AT sasakiosamu xenotransplantationelicitssalienttumorigenicityofadulttcellleukemiaderivedcellsviaaberrantaktactivation
AT satohkennichi xenotransplantationelicitssalienttumorigenicityofadulttcellleukemiaderivedcellsviaaberrantaktactivation
AT tanakanobuyuki xenotransplantationelicitssalienttumorigenicityofadulttcellleukemiaderivedcellsviaaberrantaktactivation
AT harigaehideo xenotransplantationelicitssalienttumorigenicityofadulttcellleukemiaderivedcellsviaaberrantaktactivation
AT sugamurakazuo xenotransplantationelicitssalienttumorigenicityofadulttcellleukemiaderivedcellsviaaberrantaktactivation