Individual transcriptional activity of estrogen receptors in primary breast cancer and its clinical significance

Abstract

To predict the efficacy of hormonal therapy at the individual-level, immunohistochemical methods are used to analyze expression of classical molecular biomarkers such as estrogen receptor (ER), progesterone receptor (PgR), and HER2. However, the current diagnostic standard is not perfect for the individualization of diverse cases. Therefore, establishment of more accurate diagnostics is required. Previously, we established a novel method that enables analysis of ER transcriptional activation potential in clinical specimens using an adenovirus estrogen response element–green fluorescence protein (ERE-GFP) assay system. Using this assay, we assessed the ERE transcriptional activity of 62 primary breast cancer samples. In 40% of samples, we observed that ER protein expression was not consistent with ERE activity. Comparison of ERE activity with clinicopathological information revealed that ERE activity was significantly correlated with the ER target gene, PgR, rather than ER in terms of both protein and mRNA expression. Moreover, subgrouping of Luminal A-type breast cancer samples according to ERE activity revealed that ERα mRNA expression correlated with ER target gene mRNA expression in the high-, but not the low-, ERE-activity group. On the other hand, the low-ERE-activity group showed significantly higher mRNA expression of the malignancy biomarker Ki67 in association with disease recurrence in 5% of patients. Thus, these data suggest that ER expression does not always correlate with ER transcriptional activity. Therefore, in addition to ER protein expression, determination of ERE activity as an ER functional marker will be helpful for analysis of a variety of diverse breast cancer cases and the subsequent course of treatment.

Resolvin D2 Supports MCF-7 Cell Proliferation via Activation of Estrogen Receptor

“…Furthermore, RvD2 concentration dependently increased ERE-SEAP transcriptional activity in ER-positive breast tumor cell lines (MCF-7, T47D, BT474) and in an ovarian tumor cell line (SKOV3). The enhancement of ERE transactivation was shown to have pathophysiological relevance, as it was paralleled by upregulation of GREB1 and PGR mRNA levels, well characterized ERE-containing estrogen-inducible genes (Deschênes et al, 2007;Gohno et al, 2012). The specificity of this phenomenon was confirmed by the observation that the RvD2 precursor docosahexaenoic acid did not have any impact on MDA-MB-231 and MCF-7 cell proliferation or ERE transactivation (data not shown).…”

High Level of Progesteron Receptor Membrane Component 1 (PGRMC 1) in Tissue of Breast Cancer Patients is Associated with Worse Response to Anthracycline-Based Neoadjuvant Therapy

“…Comparison of IRS of PGRMC1 and pPGRMC1 with IRS of ERα, PR, total ERβ, Ki-67 and HER2/neu revealed a significant correlation of PGRMC1 and pPGRMC1 expression solely with ERβ expression. Interestingly, most clinical studies found that high expression of ERβ-like proteins is associated with a better clinical outcome although some studies do suggest otherwise [43][44][45].…”

Utility of Ki67 labeling index, cyclin D1 expression, and ER-activity level in postmenopausal ER-positive and HER2-negative breast cancer with neoadjuvant chemo-endocrine therapy

“…Transfection of an adenovirus vector carrying an estrogen-response element-green fluorescent protein gene (Ad-ERE-GFP) was used to evaluate the level of ER activity. The methodology of this assay has been previously described in detail [16, 17]. Briefly, fresh tumor samples isolated through core needle biopsy were collected.…”