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

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• 作者：Kazunori Yamaguchi ; Tomoka Takanashi ; Kentaro Nasu ; Keiichi Tamai ; Mai Mochizuki ; Ikuro Satoh ; Shoji Ine ; Osamu Sasaki ; Kennichi Satoh ; Nobuyuki Tanaka ; Hideo Harigae and Kazuo Sugamura
• 刊名：Cancer Science
• 出版年：2016
• 出版时间：May 2016
• 年：2016
• 卷：107
• 期：5
• 页码：638-643
• 全文大小：571K
• ISSN：1349-7006

文摘

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.