Analysis of endometrial cancer development
| Project/Area Number |
17390452
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Obstetrics and gynecology
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| Research Institution | Kyushu University |
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Principal Investigator |
KATO Kiyoko Kyushu University, the Medical Institute of Bioregulation, Lecturer (10253527)
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| Co-Investigator(Kenkyū-buntansha) |
HAYASHI Shinichi Tohoku University, Faculty of Medicine, Professor (60144862)
WAKE Norio KYUSHU UNIVERSITY, Faculty of Medicine, Professor (50158606)
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| Project Period (FY) |
2005 – 2007
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| Project Status |
Completed (Fiscal Year 2007)
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| 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)
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| Keywords | endometrial cancer / endometrium / stem cell / molecular target therapy / estrogen receptor / エストロゲンレセフター |
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| 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.
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Report
(4 results)
Research Products
(50 results)
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[Journal Article] Characterization of side population cells in human normal endometrium2007
Author(s)
K., Kato, M., Yoshimoto, K., Kato, S., Adachi, A., Yanmayoshi, T., Arima, K., Asanoma, S., Kyo, T., Nakahata, N., Wake
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Journal Title
Human Reproduction 22
Pages: 1214-23
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] An inhibitory effect on cell proliferation by blockage of the MAPK/ Estrogen Receptor / MDM2 signal pathway in gynecologic cancer2007
Author(s)
S., Suga, K., Kato, A., Yamayoshi, S., Adachi, K., Asanoma, S., Yamaguchi, T., Arima, K., Kinoshita, N., Wake
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Journal Title
Gynecologic Oncology 105
Pages: 341-350
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Specific apotosis induction in HPV-positive cervical carcinoma cells by photodynamic antisense regulation2007
Author(s)
A., Yamayoshi, K., Kato, S., Suga, A., Ichinose, T., Arima, T., Matsuda, H., Kato, A., Murakami, N., Wake
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Journal Title
oligonucleotides 17
Pages: 66-79
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] 「研究成果報告書概要(欧文)」より2007
Author(s)
K., Kato, Y., Tanaka, N., Yamamoto, M., Umesaki, S., Uchida, N., Wake
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Journal Title
Osteoporosis Japan 15
Pages: 88-90
Related Report
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[Journal Article] HOP/NECC1, a novel regulator of mouse trophoblast differentiation2007
Author(s)
K., Asanoma, H., Kato, S., Yamaguchi, CH., Shin, ZP., Liu, K., Kato, T., Inoue, Y., Miyanari, K., Yoshikawa, K., Sonoda, K., Fukushima, N., Wake
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Journal Title
J Biol Chem 17
Pages: 24065-74
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Expression of progesterone receptor B is associated with G0/G1 arrest of the cell cycle and growth inhibition in NIH3T3 cells2005
Author(s)
Horiuchi, S., Kato, K., Suga, S., Takahashi, A., Ueoka, Y., Arima, T., Nishida, JI., Hachisuga, T., Kawarabayashi, T., Wake, N
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Journal Title
Exp Cell Res 305
Pages: 233-243
Description
「研究成果報告書概要(欧文)」より
Related Report
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[Journal Article] Epigenetic silencing of the imprinted gene ZAC by DNA methylation is an early event in the progression of human ovarian cancer2005
Author(s)
Kamikihara, T., Arima, T., Kato, K., Matsuda, T., Kato, H., Douchi, T., Nagata, Y., Wake, N
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Journal Title
International Journal of Cancer 115
Pages: 690-700
Description
「研究成果報告書概要(欧文)」より
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[Journal Article] Medroxyprogesterone acetate inhibits proliferation of colon cancer cell lines by modulating cell cycle-related protein expression
Author(s)
Y., Tanaka, K., Kato, R., Mibu, S., Uchida, K., Asanoma, K., Hashimoto, M., Nozaki, N., Wake
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Description
「研究成果報告書概要(欧文)」より
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[Presentation] 子宮体癌細胞の stem like cell の同定と生物学的特性の解析2007
Author(s)
K., Kato, T., Ohgami, S., Yamaguchi, T., Yoneda, K., Asanoma, N., Wake
Organizer
59th Annual Congress of the Japan Society of Obstetrics and Gynecology
Place of Presentation
Kyoto, Japan
Description
「研究成果報告書概要(欧文)」より
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