Project/Area Number |
12671627
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Obstetrics and gynecology
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Research Institution | Kitasato University |
Principal Investigator |
KURAMOTO Hiroyuki Kitasato University School of Allied Health Sciences, Professor, 医療衛生学部, 教授 (80050491)
|
Co-Investigator(Kenkyū-buntansha) |
IMAI Manami Kitasato University School of Medicine, Fellow, 医学部, 助手 (00276073)
JOBO Toshiko Kitasato University School of Medicine, Assistant Prof., 医学部, 講師 (80110873)
WATANABE Jun Kitasato University School of Medicine, Assistant Prof., 医学部, 講師 (10201188)
HATTORI Manabu Kitasato University School of Allied Health Sciences, Fellow, 医療衛生学部, 助手 (60276186)
KANAI tadayuki Kitasato University School of Medicine, Fellow, 医学部, 助手 (10276074)
佐藤 倫也 北里大学, 医学部, 助手 (20235427)
大野 英治 北里大学, 医療衛生学部, 助教授 (40276176)
秦 宏樹 北里大学, 医学部, 講師 (30146451)
|
Project Period (FY) |
2000 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2002: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 2001: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 2000: ¥1,700,000 (Direct Cost: ¥1,700,000)
|
Keywords | endometrial cancer / cell cycle / p53 transfection / VEGF / cyclin / p27 / PTEN / skp2 / 子宮内膜癌 / 子宮内膜増殖症 / 子宮内膜 / P27 / SKP-2 / P-14^<ARF> / P53遺伝子導入 / cyclin E / cyclin D1 / 細胞周期関連因子 / 予後因子 / cdk-2 / Ki-67 / p53 |
Research Abstract |
The aim of the study is to clarify the correlation of gene mutation and its expression with endometrial carcinoma in relation to carcinogenesis and prognosis of the tumor. The materials are the surgical histology specimens and cell lines in vitro. 1) VEGF expression is correlated with p53 expression. When wild p53 gene was transfected into p53-mutated HEC-50B cells, VEGF expression was down regulated. 2) P53 expression was elevated in p53-mutated cells and labeling index more than 45% indicated existence of the mutation. 3) Expressions of cell cycle regulators, including Ki-67, Cyclins E, D1, A and PTEN were correlated with those of higher-grade endometrial carcinoma, whereas p14^<ARF> was inversely higher in low grade. Expressions of almost all regulators were correlated from each other. In hyperplasia, cyclin D1, A and PTEN were expressed more intensively than normal endometrium, but less than carcinoma. In contrast, cyclin E was not expressed in hyperplasia. 4) P27 did not express in proliferative phase, but in secretary phase. In carcinomas, it expressed more intensively in higher grade, seemingly loosing growth-suppressive function. Skp2, inactivating factor of p27, was activated in high-grade carcinoma. In well-differentiated carcinoma cells (HEC-265) that possess PR elevated p27, when progestin was given, preserving the reactivity of normal endometrium. In effective group of patients who had progestin therapy, p27 expression was persistent after 13 weeks of the therapy. P27 can be a predictor of effectiveness for progestin therapy.
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