Development of novel Myc and K-Ras targeted therapies for the treatment of lung cancer
| Project/Area Number |
21591814
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Thoracic surgery
|
|---|
| Research Institution | Kawasaki Medical School (2010-2011)
Okayama University (2009) |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
MATSUOKA Jyunji 岡山大学, 大学院・医・歯薬学総合研究科, 教授 (30332795)
YAMATSUJI Tomoki 川崎医科大学, 医学部, 准教授 (40379730)
NAOMOTO Yoshio 川崎医科大学, 医学部, 教授 (00237190)
|
|---|
| Project Period (FY) |
2009 – 2011
|
| Project Status |
Completed (Fiscal Year 2011)
|
| Budget Amount *help |
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2010: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
|
|---|
| Keywords | 肺癌 / Myc / K-Ras / アデノウイルスベクター |
|---|
| Research 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.
|
Report
(4 results)
Research Products
(5 results)
