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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...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2016
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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 |
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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 |
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