The changes of estrogen receptor-β variants expression in breast carcinogenesis: Decrease of estrogen receptor-β2 expression is the key event in breast cancer development

Backgound and Objectives: Although more than five variant forms of estrogen receptor-β (ERβ) have been identilied, their role has not been identified. This study was carried out to investigate the changes of ERβ variants in breast cancer development. Methods: Using reverse transcription polymerase chain reaction (RT-PCR) and triple primer PCR (TP-PCR), the expression levels of ERβ variants mRNA were measured in 66 paired normal and cancer tissues. The relative expression level of ERβ variants were compared between normal and cancer tissues, and also compared according to various clinicopathological parameters. Results: Among ERβ variants, ERβ2 and ERβ5 consist of the major proportion of ERβ expression both in normal and cancer tissues. The ERβ and ERβ2 expression levels decreased significantly in the cancers compared with corresponding normal tissues, particularly in ERα-expressing cancers. However, ERβ5 expression level increased significantly in the cancers, especially in those of postmenopausal patients. The relative increase of ERβ5 expression in cancer tissues was associated with favorable differentiation. Conclusions: Decrease of ERβ2 is thought to be the key reason for the decrease in ERβ expression in cancer tissues, and it is particularly associated with the development of ERα-expressing breast cancer.