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

Kazunori Yamaguchi, Tomoka Takanashi, Kentaro Nasu, Keiichi Tamai, Mai Mochizuki, Ikuro Satoh, Shoji Ine, Osamu Sasaki, Kennichi Satoh, Nobuyuki Tanaka, Hideo Harigae, Kazuo Sugamura

Research output: Contribution to journalArticle

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Abstract

The transplantation of human cancer cells into immunodeficient NOD/SCID/IL-2Rγcnull (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. In this study we were able to generate highly tumorigenic sublines from ATL-derived cell lines through serial xenotransplantation in immunodeficient NOG mice. We found aberrant activation of AKT signaling plays a pivotal role in the tumorigenic potential of the ATL cells.

Original languageEnglish
Pages (from-to)638-643
Number of pages6
JournalCancer science
Volume107
Issue number5
DOIs
Publication statusPublished - 2016 May 1

Keywords

  • Adult T-cell leukemia
  • Proto-oncogene protein Akt
  • Severe combined immunodeficient mice
  • Tumor-initiating cells
  • Xenotransplantation

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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  • Cite this

    Yamaguchi, K., Takanashi, T., Nasu, K., Tamai, K., Mochizuki, M., Satoh, I., Ine, S., Sasaki, O., Satoh, K., Tanaka, N., Harigae, H., & Sugamura, K. (2016). Xenotransplantation elicits salient tumorigenicity of adult T-cell leukemia-derived cells via aberrant AKT activation. Cancer science, 107(5), 638-643. https://doi.org/10.1111/cas.12921