ESR1 gene amplification: another mechanism regulating the cellular levels of ERα

Abstract

We read with great interest the Review (The different roles of ER subtypes in cancer biology and therapy. Nature Rev. Cancer 11, 597–608 (2011))1 by Thomas and Gustafsson, in which the authors addressed the mechanisms of action and regulation of oestrogen receptors (ERs), the distinct biological effect of ER isoforms, and the roles of ERs in cancer prognosis and targeted therapies. Regarding the regulation of cellular levels of ERs, the authors systemically stated the potential mechanisms, including promoter methylation, post-transcriptional regulation by specific microRNAs and proteasome-mediated degradation of ER proteins. Although the aforementioned mechanisms are the main pathways of ER regulation, the complete mechanisms of ER upregulation are still not fully understood. One mechanism that may lead to the overexpression of a given gene in neoplastic cells is gene amplification, and ESR1 gene amplification has been observed in some cancer cells2. We believe that this issue, which is not mentioned in the Review, deserves to be discussed when illustrating the mechanisms of upregulation of ERα.