PT  - JOURNAL ARTICLE
AU  - Evrim Erdemoglu
AU  - Mehmet Güney
AU  - Gülnur Take
AU  - Seren Gülşen Giray
AU  - Tamer Mungan
TI  - RAD001 (Everolimus) Can Prevent Tamoxifen-Related Endometrial and Stromal Hyperplasia
AID  - 10.1111/IGC.0b013e3181a1a334
DP  - 2009 Mar 01
TA  - International Journal of Gynecologic Cancer
PG  - 375--379
VI  - 19
IP  - 3
4099  - http://ijgc.bmj.com/content/19/3/375.short
4100  - http://ijgc.bmj.com/content/19/3/375.full
SO  - Int J Gynecol Cancer2009 Mar 01; 19
AB  - The mechanism of tamoxifen-associated endometrial hyperplasia and cancer is not elicited. RAD001 inhibits a target protein in phosphatidyl kinase pathway, which is involved in endometrial hyperplasia and cancer. We investigated whether endometrial hyperplasia can be prevented through inhibition of the target of rapamycin by RAD001. Sixty BALB/c mice underwent oophorectomy and were divided into 6 groups: group 1, placebo group; group 2, tamoxifen-treated (4 mg/kg per 24 hours); group 3, estradiol-treated (4 mg/kg per 24 hours); group 4, RAD001-treated (1.5 mg/kg per 24 hours); group 5, tamoxifen (4 mg/kg per 24 hours)-and-RAD001 (1.5 mg/kg per 24 hours)-treated; and group 6, estradiol (4 mg/kg per 24 hours)-and-RAD001 (1.5 mg/kg per 24 hours)-treated. The count of glands, the length of epithelium, and immunohistochemical staining of proliferating cell nuclear antigen were analyzed. The count of total glands and the epithelial length were 30.8 (7.1) and 126 (43.4) μm, 53 (8.1) and 162.5 (34.8) μm, 65.2 (13.6) and 401.4 (44.0) μm, and 82.0 (5.2) and 444.7 (57.8) μm in the placebo-, the RAD001-, the tamoxifen-, and the estradiol-treated groups, respectively (P < 0.05). Although addition of RAD001 to estradiol did not decrease the count of total glands and the epithelial length, addition of RAD001 to tamoxifen did (43.3 [13.3] and 218.0 [29.2] μm, P < 0.05). The immunoreactive score of proliferating cell nuclear antigen is significantly decreased by the addition of RAD001 to either tamoxifen or estradiol in the epithelial and glandular cells. RAD001 can prevent tamoxifen-associated and estrogen-related endometrial hyperplasias in mice. RAD001 also decreases stromal cell proliferation in the tamoxifen-treated mice.