AMPD3 is associated with the malignant characteristics of gastrointestinal stromal tumors

Wong,Meihong; Funasaka,Kohei; Obayashi,Tomohiko; Miyahara,Ryoji; Hirooka,Yoshiki; Hamaguchi,Michinari; Goto,Hidemi; Senga,Takeshi

doi:10.3892/ol.2016.5532

AMPD3 is associated with the malignant characteristics of gastrointestinal stromal tumors

Authors:
- Meihong Wong
- Kohei Funasaka
- Tomohiko Obayashi
- Ryoji Miyahara
- Yoshiki Hirooka
- Michinari Hamaguchi
- Hidemi Goto
- Takeshi Senga
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Affiliations: Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya 466‑8550, Japan, Division of Cancer Biology, Nagoya University Graduate School of Medicine, Nagoya 466‑8550, Japan
Published online on: December 23, 2016 https://doi.org/10.3892/ol.2016.5532
Pages: 1281-1287

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Abstract

Gastrointestinal stromal tumors (GISTs) are mesenchymal tumors of the gastrointestinal tract. It is well known that activating mutations in the receptor tyrosine kinases KIT and platelet-derived growth factor receptor-α have essential roles in the pathogenesis of GISTs. The activation of these receptor protein kinases triggers multiple signaling pathways that promote cell proliferation and survival; however, the exact mechanism by which the activation of these kinases promotes the progression of GISTs remains uncertain. The aim of the present was to search for genes that are associated with the progression of GIST. The present study used reverse transcription-quantitative polymerase chain reaction to demonstrate that adenosine monophosphate deaminase 3 (AMPD3) was highly expressed in GISTs. Furthermore, transfection of GIST-T1 cells with KIT-specific small interfering RNA (siRNA) demonstrated that the expression of AMPD3 was dependent on KIT expression, while the depletion of AMPD3 in human GIST‑T1 cells using AMPD3-specific siRNA resulted in the suppression of cell migration and invasion. In addition, AMPD3 depletion sensitized GIST‑T1 cells to the tyrosine kinase inhibitor imatinib. The results of the present suggested that the combined inhibition of tyrosine kinases and AMPD3 may be effective for the treatment of GISTs.

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