Altered expression pattern of alternatively spliced estrogen receptor β transcripts in breast carcinoma

Dysregulation of total estrogen receptor β (ERβ) expression has been implicated in breast tumorigenesis. The ERβ gene yields five exon 8 alternatively spliced transcripts (ERβ1–5), which encode proteins with different C-terminal amino acids. Individual expression analysis of these transcripts may provide new insights into estrogen signaling in breast cancer. We measured mRNA levels of total ERβ and its five isoforms in normal tissues, breast carcinomas from post-menopausal patients, and breast cancer cell lines by means of real-time reverse transcription-polymerase chain reaction and fluorescent fragment analysis. In various normal human tissues, ERβ1–5 isoforms displayed different qualitative and quantitative expression patterns that were consistent with previous reports. Total ERβ mRNA levels were significantly lower in breast tumors than in normal breast tissues (38-fold lower, P<0.001), mainly due to lower expression of ERβ1 and ERβ2 (ERβ5 expression was similar in the two tissue types). This altered expression pattern of ERβ isoforms in breast cancer should be taken into account in future ERβ-based clinical applications.