Expression of Cyclin D1, Cyclin E, p21Cip1 and p27Kip1 in Chemically Induced Rat Mammary Tumor Treated with Tamoxifen and Transforming Growth Factor-β1
장석용, Park Jae-Hum, 조미연, 김기권, 김정란,
소속 상세정보
장석용 ( Jang Suk-Yong )
동국대학교 의과대학 병리학교실
( Park Jae-Hum )
동국대학교 의과대학 병리학교실
조미연 ( Cho Mee-Yon )
연세대학교 원주의과대학 병리학교실
김기권 ( Kim Ki-Kwon )
동국대학교 의과대학 병리학교실
김정란 ( Kim Jung-Ran )
동국대학교 의과대학 병리학교실
KMID : 0357920010350020151
Abstract
Background: Tamoxifen (TAM) inhibits the action of estrogen by binding to estrogen receptors, and also has non-estrogen receptor mediated cytostatic activities. Transforming growth factor-β1 (TGF-β1) inhibits the proliferation of many other cell types, such as epithelial, hematopoietic and endothelial cells.
Methods: We investigated the effects of tamoxifen on the growth of 7,12-dimethylbenz(a)anthracene (DMBA)-induced rat mammary tumors and the expression of cyclin D1, cyclin E, p21Cip1, and p27Kip1 by performing immunohistochemistry and Western blot analysis, and studied whether TGF-β1 injection amplified the effects of TAM. When tumor size reached between 10-15 mm in the largest dimension, the rats were divided into 3 groups: DMBA-control group (n=12), DMBA-TAM group (n=14) and DMBATAM plus TGF-β1 group (n=5).
Results: The consecutive administration of TAM markedly decreased the tumor development compared with the DMBA-control group. The DMBA-TAM and DMBA-TAM plus TGF-β1 groups showed decreased expression of bromodexoyuridine, cyclin D1, cyclin E, and p21Cip1 when compared with those of the DMBA-control group. On the other hand, the labeling index of p27Kip1 was higher in the DMBA-TAM plus TGF-β1 group than in the DMBA-control group.
Conclusions: TAM suppresses tumor development, which may be associated with down-expression of cyclin D1 and cyclin E, and overexpression of p27Kip1, and addition of TGF-β1 does not influence tumor development treated by TAM.
키워드
Breast;Neoplasms;Cell cycle;Tamoxifen;Transforming growth factor beta
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