2. Academic Validation
  3. Xenotransplantation elicits salient tumorigenicity of adult T-cell leukemia-derived cells via aberrant AKT activation

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

  • Cancer Sci. 2016 May;107(5):638-43. doi: 10.1111/cas.12921.
Kazunori Yamaguchi 1 2,  Tomoka Takanashi 1,  Kentaro Nasu 1 3,  Keiichi Tamai 2 4,  Mai Mochizuki 1 2,  Ikuro Satoh 2 5,  Shoji Ine 6,  Osamu Sasaki 6,  Kennichi Satoh 2 7,  Nobuyuki Tanaka 2 4,  Hideo Harigae 3,  Kazuo Sugamura 1
Affiliations

Affiliations

  • 1 Division of Molecular and Cellular Oncology, Miyagi Cancer Center Research Institute, Natori, Japan.
  • 2 Department of Cancer Science, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • 3 Department of Hematology and Rheumatology, Tohoku University Graduate School of Medicine, Sendai, Japan.
  • 4 Division of Cancer Biology and Therapeutics, Miyagi Cancer Center Research Institute, Natori, Japan.
  • 5 Department of Pathology, Miyagi Cancer Center, Natori, Japan.
  • 6 Division of Hematology, Miyagi Cancer Center, Natori, Japan.
  • 7 Division of Cancer Stem Cells, Miyagi Cancer Center Research Institute, Natori, Japan.
PMID: 26928911 DOI: 10.1111/cas.12921
Abstract

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.

Keywords

Adult T-cell leukemia; proto-oncogene protein Akt; severe combined immunodeficient mice; tumor-initiating cells; xenotransplantation.

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