Amyloid precursor protein cooperates with c-KIT mutation/overexpression to regulate cell apoptosis in AML1-ETO-positive leukemia via the PI3K/AKT signaling pathway

  • Authors:
    • Guopan Yu
    • Changxin Yin
    • Ling Jiang
    • Zhongxin Zheng
    • Zhixiang Wang
    • Chunli Wang
    • Hongsheng Zhou
    • Xuejie Jiang
    • Qifa Liu
    • Fanyi Meng
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  • Published online on: July 21, 2016     https://doi.org/10.3892/or.2016.4963
  • Pages: 1626-1632
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Abstract

It has been reported that amyloid precursor protein (APP) promotes cell proliferation and metastasis in various types of solid cancers. In our previous study, we showed that APP is highly expressed and regulates leukemia cell migration in AML1‑ETO-positive (AE) leukemia. Whether APP is involved in the regulation of AE leukemia cell proliferation or apoptosis is unclear. In the present study we focused on the correlation of APP with c-KIT mutation/overexpression and cell proliferation and apoptosis in AE leukemia. APP and c-KIT expression detected by quantitative real-time (qPCR) method, and c-KIT mutations screened using PCR in bone marrow cells from 65 patients with AE leukemia before their first chemotherapy, were simultaneously assessed. Furthermore, the Kasumi-1 cell line was chosen as the cell model, and the APP gene was knocked down using siRNA technology. The correlation of cell cycle distribution and apoptosis and c-Kit expression with APP expression levels, as well as the regulation of the PI3K/AKT signaling pathway by APP were analyzed in the Kasumi-1 cell line. The results showed that peripheral white blood cell counts (P=0.008) and bone marrow cellularity (P=0.031), but not bone marrow blasts, were correlated with APP expression. Moreover, the patients with APP high expression had a significantly higher incidence of c-KIT mutations (P<0.001) and increased levels of c-KIT expression (P=0.001) and poorer disease outcome. In the Kasumi-1 cell line, as compared with the wild-type and negative control cells, cell apoptosis, both early (P<0.001) and late (P<0.001), was significantly increased when the APP gene was knocked down, concomitant with reduced levels of anti-apoptotic protein Bcl-2 and increased levels of caspase-3 and -9, however, no apparent change was observed in the cell cycle distribution (P>0.05). Moreover, the knockdown of APP markedly decreased c-KIT expression at both the transcription (as evidenced by qPCR analysis) and translation (as confirmed by CD117 assay and western blot analysis) levels, as well as p-AKT and its downstream targets including NF-κB, p53 and Bcl-2. In conclusion, APP may cooperate with c-KIT mutation/overexpression in the regulation of cell apoptosis but not proliferation in AE leukemia via the PI3K/AKT signaling pathway.
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September-2016
Volume 36 Issue 3

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Yu G, Yin C, Jiang L, Zheng Z, Wang Z, Wang C, Zhou H, Jiang X, Liu Q, Meng F, Meng F, et al: Amyloid precursor protein cooperates with c-KIT mutation/overexpression to regulate cell apoptosis in AML1-ETO-positive leukemia via the PI3K/AKT signaling pathway. Oncol Rep 36: 1626-1632, 2016
APA
Yu, G., Yin, C., Jiang, L., Zheng, Z., Wang, Z., Wang, C. ... Meng, F. (2016). Amyloid precursor protein cooperates with c-KIT mutation/overexpression to regulate cell apoptosis in AML1-ETO-positive leukemia via the PI3K/AKT signaling pathway. Oncology Reports, 36, 1626-1632. https://doi.org/10.3892/or.2016.4963
MLA
Yu, G., Yin, C., Jiang, L., Zheng, Z., Wang, Z., Wang, C., Zhou, H., Jiang, X., Liu, Q., Meng, F."Amyloid precursor protein cooperates with c-KIT mutation/overexpression to regulate cell apoptosis in AML1-ETO-positive leukemia via the PI3K/AKT signaling pathway". Oncology Reports 36.3 (2016): 1626-1632.
Chicago
Yu, G., Yin, C., Jiang, L., Zheng, Z., Wang, Z., Wang, C., Zhou, H., Jiang, X., Liu, Q., Meng, F."Amyloid precursor protein cooperates with c-KIT mutation/overexpression to regulate cell apoptosis in AML1-ETO-positive leukemia via the PI3K/AKT signaling pathway". Oncology Reports 36, no. 3 (2016): 1626-1632. https://doi.org/10.3892/or.2016.4963