| Project/Area Number |
17390452
|
|---|
| Research Category |
Grant-in-Aid for Scientific Research (B)
|
| Allocation Type | Single-year Grants |
|---|
| Section | 一般 |
|---|
| Research Field |
Obstetrics and gynecology
|
|---|
| Research Institution | Kyushu University |
|---|
Principal Investigator |
KATO Kiyoko Kyushu University, the Medical Institute of Bioregulation, Lecturer (10253527)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Shinichi Tohoku University, Faculty of Medicine, Professor (60144862)
WAKE Norio KYUSHU UNIVERSITY, Faculty of Medicine, Professor (50158606)
|
|---|
| Project Period (FY) |
2005 – 2007
|
| Project Status |
Completed (Fiscal Year 2007)
|
| Budget Amount *help |
¥16,740,000 (Direct Cost: ¥15,600,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2007: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000)
Fiscal Year 2006: ¥3,800,000 (Direct Cost: ¥3,800,000)
Fiscal Year 2005: ¥8,000,000 (Direct Cost: ¥8,000,000)
|
|---|
| Keywords | endometrial cancer / endometrium / stem cell / molecular target therapy / estrogen receptor / エストロゲンレセフター |
|---|
| Research Abstract |
1. We previously demonstrated that that the Ras/ER/MDM2 pathway was critical for NIH3T3 cell transformation. In this study, we examined the effect of blocking this pathway on cell growth in gynecologic cancer cells. (1) The MDM2 level was enhanced in cancer cells compared with normal cells. Treatment with MEK inhibitor (U0126) resulted in a reduced MDM2 level, enhanced p53 and p21 levels and inhibited cell growth by the induction of premature senescence. (2) The effect of MEK inhibitor on cell growth was affected by ER levels and functions. Treatment with low-dose MEK inhibitor in combination with anti-estrogen (ICI182,780) had a more inhibitory effect on cell growth compared to treatment with MEK inhibitor or anti-estrogen alone in cancer cells. Down-regulation of the MDM2 level by siRNA resulted in the inhibition of growth in cancer cells.
2. We isolated SP cells from the human endometrium and analyzed their properties. SP cells were present in normal human endometrial cells. Most SP cells were enriched in the CD9-CD13- fraction. These SP cells showed long-term repopulating properties and produced gland(CD9 positive)- and stroma(CD13 positive)-like cells. SP cells in the human endometrium can function as progenitor cells. This is the first report of the phenotype of SP cells from normal human endometrial cells.
3. We determined the correlation between PR-B expression and cell cycle progression. In synchronized NIH3T3 cells, we found an increase in PR-B protein and p27 CDK inhibitor levels in the G0/G1 phase and a reduction due to redistribution in the S and G2/M phases. The decrease in the PR-B levels caused by anti-sense oligomers or siRNA corresponded to the reduction in p27 levels. PR-B overexpression by adenovirus infection induced p27 and suppressed cell growth. Finally, we showed that induction of PR-B involved in the regulation of NIH3T3 cell proliferation was estrogen(E2)/estrogen receptor (ER) independent.
|
