| Project/Area Number |
08671881
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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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 | Gifu University |
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Principal Investigator |
FUJIMOTO Jiro School of Medicine, Gifu University Assistant Professor, 医学部・附属病院, 講師 (80199372)
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| Co-Investigator(Kenkyū-buntansha) |
TAMAYA Teruhiko School of Medicine, Gifu University Professor, 医学部, 教授 (70079870)
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| Project Period (FY) |
1996 – 1998
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| Project Status |
Completed (Fiscal Year 1998)
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| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1998: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1997: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1996: ¥700,000 (Direct Cost: ¥700,000)
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| Keywords | invasion and metastasis / sex steroids / steroid receptors / splicing variants / mutation / angiogenesis / angiogenic factors / female genital tract cancers / 婦人科癌 / 浸潤・転移 / 核内受容体 / カドヘリン / FGF / 子宮内膜癌 / エストロゲン / プロゲスチン / E-カドヘリン / PAI-1 / TNP470 |
|---|
| Research Abstract |
Expression of the progesterone-refractory estrogen-dependent oncogenes c-Ha-ras, c-fos and c-jun in uterine endometrial cancers is recognized as a transformed phenotype. During advancement of female genital tract cancers, relative overexpression of estrogen receptor exon 5 splicing variant (ER E5SV) as a transcriptional activator and damaged expression of progesterone receptor form A (PR-A) as a transcriptional repressor might contribute to metastasis of the cancers. Furthermore, estrogen might enhance various steps of invasion and metastasis of some uterine endometrial cancers, and progestin could inhibit the estrogen-related events, especially tumor-derived angiogenesis. The irregular response to progestins in tumor growth might be caused by the damage to PR-A expression. The status of progesterone receptor form B (PR-B) dominant expression without PR-A transcriptional repression relates to some tumorigenesis, On the other hand, it is not clear whether progestin is effective on the tumor derived-angiogenesis in PR-mutated female genital tract cancers or not. Most Likely, progestin treatment as an anti-angiogenic therapy would be less effective in the PR-mutated tumors. The data presented herein should spur us towards attempting gene therapy which would neutralize steroid receptor gene expressions as a treatment against female genital tract cancers. Meanwhile, various anti-angiogenic inhibitors must be used in progestin-refractory and progestin-dependent tumors.
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