ETV6/ARG oncoprotein confers autonomous cell growth by enhancing c-Myc expression via signal transducer and activator of transcription 5 activation in the acute promyelocytic leukemia cell line HT93A

Abstract

We investigated the role of ETV6/ARG fusion gene by exposing the HT93A cell line to nilotinib. HT93A cells were cultured with or without nilotinib ± 50 ng/mL of granulocyte colony-stimulating factor (G-CSF). Nilotinib treatment inhibited cell growth by increasing the percentage of cells in G0/G1 phase through the decrease of phosphorylated signal transducer and activator of transcription 3 (STAT3) (Y705), STAT5 (Y694) and c-Myc expression. After stimulation with G-CSF, STAT5 but not STAT3 was significantly phosphorylated in both nilotinib-treated and untreated cells. Moreover, combination therapy with nilotinib and G-CSF returned the expression level of c-Myc, cell growth and cell cycle distribution to the control level. These findings suggest that the ETV6/ARG oncoprotein contributes to autonomous cell growth by compensating for the requirement of growth factor through activating STAT5 signaling, which leads to the up-regulation of c-Myc. Our data suggest that ETV6/ARG oncoprotein is a potential target in the treatment of leukemia.

Keywords::

• ETV6/ARG
• signal transducer and activator of transcription
• c-Myc
• HT93A

Acknowledgements

This work was funded in part by Novartis and Kyowa Hakko Kirin Co, Ltd. The authors thank Dr. Kenji Kishi and Dr. Yuko Sato for providing the HT93A cell line, and Ms. Eiko Ishizuka for technical assistance.

Potential conflict of interest

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