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Estrogen receptors (ERs) and the PTEN-Akt-mTor pathway are important growth regulators in human breast cancer cells, which both are known to affect response to tamoxifen therapy. Recently it was reported that ER β activates PTEN expression and tamoxifen sensitivity of human breast cancer cells. In this study we examined whether expression of ER β in turn might be affected by tumor suppressor PTEN, analyzed the effect of this interaction on tamoxifen response and the co-expression of both genes in human breast cancer samples. After siRNA-mediated PTEN knockdown, Western blot analysis revealed a reduction of ER β protein expression by 67.2% in MCF-7 cells and by 73.6% in T-47D cells (both p<0.01), results which could be verified on the mRNA level. In cells with normal PTEN and ER β status, after 6 days of treatment with 1 µM 4-OH tamoxifen, E2-driven proliferation was decreased by 64.5% in MCF-7 and by 57.7% in T-47D cells (both p<0.01). After knockdown of PTEN expression, the same concentration of 4-OH TAM reduced E2-triggered growth only by 34.9% (MCF-7) and by 41.8% (T-47D) (both p<0.01 vs control siRNA). Importantly, treatment with ER β agonist DPN (5 nM) significantly decreased the inhibitory effect of a PTEN knockdown on tamoxifen response of both cell lines (p<0.05). Additionally, Spearmańs rank association analysis of PTEN and ER β 1 mRNA levels in 115 normal and malignant breast tissue samples revealed a strong positive correlation of both genes (rho=0.6085, p<0.0001). The data of previous studies reporting an important role of ER β in tamoxifen sensitivity and our findings suggest down-regulation of ER β triggered by PTEN knockdown contributed to the decreased response of breast cancer cells to tamoxifen observed in this study. Our data also suggest expression of ER β might be maintained by tumor suppressor PTEN in human breast cancer cells.
This article was published in the following journal.
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One of the SELECTIVE ESTROGEN RECEPTOR MODULATORS with tissue-specific activities. Tamoxifen acts as an anti-estrogen (inhibiting agent) in the mammary tissue, but as an estrogen (stimulating agent) in cholesterol metabolism, bone density, and cell proliferation in the ENDOMETRIUM.
One of the ESTROGEN RECEPTORS that has marked affinity for ESTRADIOL. Its expression and function differs from, and in some ways opposes, ESTROGEN RECEPTOR BETA.
A first generation selective estrogen receptor modulator (SERM). Like TAMOXIFEN, it is an estrogen agonist for bone tissue and cholesterol metabolism but is antagonistic on mammary and uterine tissue.
One of the ESTROGEN RECEPTORS that has greater affinity for ISOFLAVONES than ESTROGEN RECEPTOR ALPHA does. There is great sequence homology with ER alpha in the DNA-binding domain but not in the ligand binding and hinge domains.
A second generation selective estrogen receptor modulator (SERM) used to prevent osteoporosis in postmenopausal women. It has estrogen agonist effects on bone and cholesterol metabolism but behaves as a complete estrogen antagonist on mammary gland and uterine tissue.
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