Project/Area Number |
13671685
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Urology
|
Research Institution | Mie University (2002) Aichi Cancer Center Research Institute (2001) |
Principal Investigator |
SUGIMURA Yoshiiki Mie University Faculty of Medicine Professor, 医学部, 教授 (90179151)
|
Co-Investigator(Kenkyū-buntansha) |
TATEMATSU Masae Aichi Cancer Center, Research Institute, Vice Director Chief of Dept of Oncological Pathology, 研究所, 副所長 (70117836)
|
Project Period (FY) |
2001 – 2002
|
Project Status |
Completed (Fiscal Year 2002)
|
Budget Amount *help |
¥2,900,000 (Direct Cost: ¥2,900,000)
Fiscal Year 2002: ¥1,400,000 (Direct Cost: ¥1,400,000)
Fiscal Year 2001: ¥1,500,000 (Direct Cost: ¥1,500,000)
|
Keywords | prostate / microdissection / prostate duct / estrogen / esterogen recetor / エストロゲン受容体ノックアウトマウス |
Research Abstract |
Ventral and dorsal-lateral prostates of adult mice treated neonatally with diethylstilbestrol (DBS), dihydrotestosterone (DHT), alone or in combination were microdissected into two-dimensional arrays to visualize ductal branching architecture. Neonatal exposure to DES markedly suppressed and modified prostatic ductal branching patterns in adulthood. This long-term effect on prostatic ductal architecture was not prevented by co-administration of DHT. Treatment with DES alone or in combination with DHT reduced the number of ductal tips and branch points in ventral and dorsal-lateral prostates and reduced the number of main ducts in the dorsal-lateral prostate. The unique effect of neonatal DES treatment was the development of abnormal epithelial nodules in the dorsal-lateral prostate, which contained a distinctly non-prostatic epithelium organized into small back to back glands having a cribriform histopathology. Immunohistochemical analysis demonstrated in newborn mouse the presence of estrogen receptor alpha (ERα) in a subset of prostatic stromal cells near the urethra and estrogen receptor beta (ERβ) in both prostatic stromal and epithelial cells. After 5 days of DES treatment ERα immunostaining was detected in both prostatic stromal and epithelial cells. Thus, neonatal treatment with DES perturbed the pattern of ductal branching in certain lobes of the mouse prostate and altered epithelial differentiation presumably via estrogen receptor signaling.
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