| Project/Area Number |
16591389
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Thoracic surgery
|
|---|
| Research Institution | Shinshu University School of Medicine |
|---|
Principal Investigator |
AMANO Jun Shinshu University, School of Medicine, MD, PhD, Professor, 医学部, 教授 (20138283)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
NAKAYAMA Jun Shinshu University, School of Medicine, MD., PhD., Professor, 医学部, 教授 (10221459)
FUJIMORI Minoru Shinshu University, School of Medicine, MD, Ph.D, Associate Professor, 医学部, 助教授 (00262725)
ITO Ken-ichi Shinshu University, School of Medicine, MD, Ph.D, Lecturer, 医学部附属病院, 講師 (10334905)
|
|---|
| Project Period (FY) |
2004 – 2005
|
| Project Status |
Completed (Fiscal Year 2005)
|
| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2005: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2004: ¥2,100,000 (Direct Cost: ¥2,100,000)
|
|---|
| Keywords | Cardiac myxoma / Wnt / β catenin signal / β catenin / APC gene / Proteoglycan / Glucosaminoglycan / Chodroitin-6-sulphate / Versican / 心臓 / 粘液腫 / Wntシグナル / βカテニン / 糖タンパク / βカテキン |
|---|
| Research Abstract |
Objective : Cardiac myxoma is of interest because of uncertain histogenesis. In this study, we showed that Wnt-1 is indispensable for the growth and survival of cardiac myxoma.
Methods and Result : Tissue samples of cardiac myxomas were obtained from 31 patients, who underwent surgical resection between 1988 and 2004 at Shinshu University School of Medicine Hospital and affiliated hospitals. In 81% of the myxoma cases, we observed β-catenin accumulation and c-myc expression in the nucleus of tumor cells using immunohistochemistry. In 71% of the myxoma cases with β-catenin accumulation, Wnt-1 overexpression was observed. To determine the cause of β-catenin accumulation, we analyzed the amplification of the Wnt-1 sequence using real time PCR and the mutations of β-catenin and APC gene using DNA sequencing and SSCP analysis, however, no amplification of the Wnt-1 sequence was detected and no mutation was found in either APC or the β-catenin gene. To examine involvement of Wnt-1 in the survival and development of cardiac myxoma, primary cultured myxoma cells were exposed to anti-Wnt-1 antibody and cellular proliferation was measured. Treatment with Wnt-1 antibody reduced the proliferation of the cultured myxoma cells. Trypan blue exclusion analysis and the examination of DNA laddering by agarose gel analysis showed that Wnt-1 antibody caused cell death and DNA fragmentation. We found that Wnt-1 antibody reduced c-myc and β-catenin expression levels using real time RT-PCR and Western blotting.
Versican having chodroitin-6-phosphate as a GAG is important for formation of vascular structures observed in cardiac myxoma, since these channel like structures are frequently observed in the same distribution of proteoglycan.
Conclusion : The results of our study strongly suggest the possibility that Wnt/β-catenin signaling may play critical roles in the tumor growth of cardiac myxoma.
|
