AMPD3 is associated with the malignant characteristics of gastrointestinal stromal tumors

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

来源：Oncology Letters, 2017, 13(3): 1281-1287.

DOI：10.3892/ol.2016.5532

• gastrointestinal stromal tumors
• KIT
• adenosine monophosphate deaminase 3
• migration
• invasion
• imatinib

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-a 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.

• 出版日期2017-3