Gene targeting therapy for oral carcinoma using adrenomedullin antagonisit.
| Project/Area Number |
16390575
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Surgical dentistry
|
|---|
| Research Institution | Hokkaido University |
|---|
Principal Investigator |
SHINDOH Masanobu Hokkaido University, Graduate School of Dental Medicine, Professor, 大学院・歯学研究科, 教授 (20162802)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KOBAYASHI Masanobu Hokkaido University, Institute for Genetic Medicine, Associate Professor, 遺伝子病制御研究所, 助教授 (80241321)
HIGASHINO Fumihiro Hokkaido University, Graduate School of Dental Medicine, Instructor, 大学院・歯学研究科, 助手 (50301891)
OHIRO Yoichi Hokkaido University, Hospital, Instructor, 助手 (40301915)
ONO Mitsunobu Hokkaido University, Graduate School of Dental Medicine, Instructor, 大学院・歯学研究科, 助手 (50281829)
TOTSUKA Yasunori Hokkaido University, Graduate School of Dental Medicine, Professor, 大学院・歯学研究科, 教授 (00109456)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥14,500,000 (Direct Cost: ¥14,500,000)
Fiscal Year 2005: ¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2004: ¥11,300,000 (Direct Cost: ¥11,300,000)
|
|---|
| Keywords | HIF-1 / Adrenomedullin / CRM1 / 口腔扁平上皮がん / リンパ節転移 |
|---|
| Research Abstract |
We have recently reported that intra-tumoral injection of adrenomedullin (AM) antagonist (AMA ; AM(22-52)) peptides significantly reduced the in vivo growth of a pancreatic cancer cell line in SCID mice. In this study, we examined the effects of intra-tumoral and intra-muscular transfers of naked DNA encoding. AMA on the in vivo growth of cancer cell lines. We demonstrated here that the intra-tumoral and intra-muscular transfers of naked DNA encoding AMA induced the regression of a pancreatic cancer cell line and a breast cancer cell line. We further demonstrated that CD31-positive cells completely disappeared from the tumor tissues treated with the intra-tumoral or intra-muscular transfer of naked DNA encoding AMA. These results suggest that the intra-tumoral or intra-muscular transfer of naked DNA encoding AMA might be a promising tool for treating cancers
E4orf6 plays an important role in the transcription of cellular and viral mRNAs. We show that E4orf6 interacts with pp32/LAMP and exports pp32/LAMP from the nucleus to the cytoplasm with its binding partner, HuR, which binds to an AU-rich element (ARE) present within many protooncogene and cytokine mRNAs. We found that ARE-mRNAs, such as c-fos,c-myc and Cox-2, were exported to and stabilized in the cytoplasm of E4orf6-expressing cells.The oncodomain of E4orf6 was necessary for both binding to pp32/LAMP and defect for ARE-mRNA. Moreover, inhibition of CRM1-dependent export pathway failed to block the export of ARE-mRNAs mediated by E4orf6. Thus, E4orf6 interacts with pp32/LAMP to modulate the fate of ARE-mRNAs by altering the CRM1-dependent export pathway.
|
Report
(3 results)
Research Products
(8 results)
