in Chemically Induced Rat Mammary Tumor Treated with Tamoxifen and Transforming Growth Factor- 1

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- 1 (TGF- 1) 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 p27 Kip1 by performing immunohistochemistry and Western blot analysis, and studied whether TGF- 1 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- 1 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- 1 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 p27 Kip1 was higher in the DMBA-TAM plus TGF- 1 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 p27 Kip1 , and addition of TGF- 1 does not influence tumor development treated by TAM.