Knockdown of PTEN decreases expression of estrogen receptor β 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. O...
Source: Steroids - Category: Drugs & Pharmacology Source Type: research