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

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.

journal_name

Anticancer Res

journal_title

Anticancer research

authors

Fukazawa T,Maeda Y,Matsuoka J,Yamatsuji T,Shigemitsu K,Morita I,Faiola F,Durbin ML,Soucek L,Naomoto Y

subject

Has Abstract

pub_date

2010-10-01 00:00:00

pages

4193-200

issue

10

eissn

0250-7005

issn

1791-7530

pii

30/10/4193

journal_volume

30

pub_type

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