| Project/Area Number |
21590995
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Respiratory organ internal medicine
|
|---|
| Research Institution | Kawasaki Medical School (2011)
Okayama University (2009-2010) |
|---|
Principal Investigator |
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KIURA Katsuyuki 岡山大学, 大学病院, 教授 (10243502)
|
|---|
| 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: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2010: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2009: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
|
|---|
| Keywords | 肺癌 / 発癌 / EGFR / 肺腺癌 / 遺伝子変異 |
|---|
| Research Abstract |
Bronchioloalveolar carcinoma(BAC) pattern is often seen at the margin of invasive adenocarcinomas. We investigated EGFR signaling abnormalities involved in the progression of adenocarcinoma. Fifty tumors were obtained from patients who underwent surgery for lung adenocarcinoma seen as dense areas in ground glass opacity on computed tomography. Six, 18, and 26 tumors<1 cm, 1-2 cm, and≧2 cm in diameter, respectively, were analyzed. Of the 24 tumors≦2 cm in diameter, nine were preinvasive and 15 were invasive. EGFR, pAKT, and pMAPK were overexpressed in the center of the adenocarcinoma compared to the BAC component by immunohistochemistry, while pSTAT3 expression was reversed. In the tumors≦2 cm in diameter, pSTAT3 expression in the central area was higher in preinvasive tumors than in invasive tumors. pSTAT3 was identified in the BAC component of 88% of the EGFR mutant(n=17) and 82% of the wild-type tumors(n=33). Transgenic mice expressing delE748-A752 EGFR and two lung cancer cell lines(PC-9 mutant and A549 wild-type EGFR) were also investigated. In transgenic mice, pSTAT3 was overexpressed in the BAC component around the adenocarcinoma center. Two lung cancer cell lines that overexpressed pSTAT3 were equally sensitive to a JAK2/STAT3 inhibitor(JSI-124). In conclusion, adenocarcinomas with a BAC component overexpressed pSTAT3 at the margin compared to the center of the tumor. Moreover, STAT3 inhibitors may have therapeutic potential in the inhibition of adenocarcinoma.
|
