The expression and function of estrogen receptor α and β in human breast cancer and its clinical application

Abstract

The overexpression of estrogen receptor α (ERα) is frequently observed in the early stage of breast cancer. We previously reported that the specific promoter of the ERα gene is responsible for this enhanced transcription of the gene, and identified the cis-acting elements which play an important role in its transcription. Furthermore, methylation of the ERα gene promoters also contribute to the regulation of gene transcription. Elucidation of these mechanisms of ERα gene expression may provide useful information for the early detection and chemoprevention of breast cancer. On the other hand, the expression of ERβ has been reported in breast cancer. We have also assessed the significance and function of ERβ and its variant types in breast cancer, and suggest that ERβ and ERα specifically suppress the function of ERα through different mechanisms. ERβ isoforms may be important functional modulators of the estrogen-signaling pathway in breast cancer cells, and might affect the clinical outcome of patients. Moreover, to address the role of these ERs on the estrogen-dependent growth of breast cancer cells and to develop a diagnostic tool, we have analyzed the gene expression profiles of estrogen-responsive genes using cDNA microarray. Based on these results, the expression of several candidate genes in breast cancer tissues were analyzed by real-time RT-PCR and by immunohistochemical techniques, in order to discover new predictive factors for the endocrine therapy of patients with breast cancer. These studies could provide new clues for the elucidation of the estrogen-dependent mechanisms of cancer and the clinical benefits for patients.