Inhibition of myc effectively targets KRAS mutation-positive lung cancer expressing high levels of Myc

Takuya Fukazawa, Yutaka Maeda, Junji Matsuoka, Tomoki Yamatsuji, Kaoru Shigemitsu, Ichiro Morita, Francesco Faiola, Mary L. Durbin, Laura Soucek, Yoshio Naomoto

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22 Citations (Scopus)

Abstract

Myc is an oncogenic transcription factor that promotes tumorigenesis. Recently, a dominant negative form of Myc (Omomyc) was shown to cause regression of lung tumors in a mouse model of lung cancer caused by KRAS mutation, suggesting that Myc might be a potential therapeutic target to treat the KRAS lung cancer. However, it is not yet known whether Omomyc can also inhibit the growth of human lung tumors that carry a similar KRAS mutation. In the present study, we demonstrate that Omomyc induces cell death of KRAS-mutated human lung adenocarcinoma A549 cells in vitro and in vivo. However, Omomyc does not induce cell death in human lung adenocarcinoma H441 cells that also carry the KRAS mutation. Interestingly, A549 cells express high levels of Myc, while H441 cells do not. Co-expression of exogenous Myc with Omomyc in H441 cells induces cell death, indicating that Omomyc requires high levels of Myc to induce cell death in KRAS mutation-positive lung adenocarcinoma. Here, we show for the first time that KRAS mutation-positive lung cancer displaying high levels of Myc could be treated by inhibiting Myc transactivation function.

Original languageEnglish
Pages (from-to)4193-4200
Number of pages8
JournalAnticancer research
Volume30
Issue number10
Publication statusPublished - Oct 2010

Keywords

  • A549
  • KRAS lung cancer
  • Myc
  • Omomyc

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Fukazawa, T., Maeda, Y., Matsuoka, J., Yamatsuji, T., Shigemitsu, K., Morita, I., Faiola, F., Durbin, M. L., Soucek, L., & Naomoto, Y. (2010). Inhibition of myc effectively targets KRAS mutation-positive lung cancer expressing high levels of Myc. Anticancer research, 30(10), 4193-4200.