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Development of cross-resistance to tamoxifen in raloxifene-treated breast carcinoma cells.
Gao ZO, Gao ZP, Fields JZ, Boman BM
Division of Genetic and Preventive Medicine, Thomas Jefferson University, Philadelphia, PA 19107, USA.
Selective estrogen receptor modifiers (SERMs) are used chronically in the treatment of breast cancer and osteoporosis but some patients become resistant, at which point second-line SERMs are considered as options.
Because the use of SERMs is increasing and breast cancer is so common, we tested the hypothesis that treatment with SERMs can induce cross-resistance to other SERMs. We used three cultured breast carcinoma cell lines (MCF-7, ZR-75-1, and T47D) which are estrogen-receptor-positive (ER+) and are prone to developing resistance to hormonal treatment.
Cell lines were exposed to increasing doses of raloxifene. Raloxifene-resistant clones were selected and tested for cross-resistance to tamoxifen. Compared to untreated cells, raloxifene-resistant clones showed an increased IC50 (reduced potency) of about 15,000-fold with no apparent change in maximal inhibition of cell growth.
These same raloxifene-resistant clones were also about 15-fold more resistant to the growth-inhibiting effects of tamoxifen.
While the resistance to tamoxifen is considerably less marked (1000-fold less), it is large enough to raise the question as to whether patients who become resistant to raloxifene will benefit by switching to tamoxifen or vice versa.
Anticancer Res 2002 May-Jun;22(3):1379-83
PMID: 12168814, UI: 22158494
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