Loss of estrogen receptor β expression in malignant human prostate cells in primary cultures and in prostate cancer tissues

The aim of this study was to investigate the expression of estrogen receptor (ER)beta and alpha genes in normal (N) and malignant (C) primary cultures of human prostate epithelial cells (PEC) and fibroblasts (PFC) and in the prostate tissue donors. Both ER beta and ER alpha messenger ribonucleic acids were found by RT-PCR analysis in six NPECs and normal prostate tissues and in only one of six CPECs and in th:e respective cancer tissue donor. The other five CPECs add related cancer tissue donors and all normal and cancer PFCs expressed ER alpha messenger ribonucleic acid alone. Immunoblot analysis, using a polyclonal anti-ER beta (C-terminal) antibody, demonstrated ERP protein in all NPEC lysates and in one of the six CPECs. ER alpha protein was expressed in both NPECs and CPECs when a polyclonal antibody directed against the ER alpha N-terminal domain was used. In contrast, En alpha protein was not detected in two of the six CPEC lysates when ER alpha C-terminal monoclonal antibodies were used. Using a set of primers designed to amplify the region from exons 6-8, RT-PCR analysis demonstrated the absence of the expected transcript in these cells. The present study shows that the ER beta gene is expressed together with ER alpha in normal prostates and NPECs, whereas it is barely detectable in prostate cancer and CPECs. Moreover, in some CPECs, the ER alpha gene may be transcribed in a changed protein, resulting from the expression of a deletion variant. Together, these data suggest that prostate malignancy is associated with a potential disorder of ER-mediated pathways.