ERα and ERβ co-expression: An indicator of aggressive tumors and hormonal sensitivity

Abstract

The estrogen receptors (ERs) ERα and ERβ are important factors in breast cancer progression. Nevertheless, the molecular interplay between ERα and ERβ and its clinical significance in breast cancer is controversial. The establishment of a clear association is required; therefore, the current study analyzed the expression patterns of ERα and ERβ in 32 breast tumor tissues using reverse transcription-quantitative polymerase chain reaction. Furthermore, human epidermal growth factor receptor 2 (HER2) and the Ki-67 status were detected by immunohistochemistry. The results revealed that the ERα and ERβ expression rates recorded were 68 and 65%, respectively. The ERα:ERβ ratio exhibited a decline along with disease progression. ERα and ERβ were found to be negatively correlated with HER2 status but positively correlated with Ki-67. Co-expression of ERα and ERβ was associated with breast cancer aggressiveness, including higher histological grade and positive nodal status, which commonly occur following the menopause. In addition, in cases where ERβ was coexpressed with ERα, HER2 expression was frequently found to be negative, whereas the Ki-67 index was upregulated. These data suggest that ERα and ERβ co-expression may be an indicator of tumor aggressiveness and the sensitivity of hormonal therapy via the downregulation of HER2.

HDAC3–ERα Selectively Regulates TNF-α-Induced Apoptotic Cell Death in MCF-7 Human Breast Cancer Cells via the p53 Signaling Pathway

“…A growing body of evidence has shown that HDAC3 inhibition accelerates p53 acetylation and stability in human cancer cells [26,27]. In breast cancer in particular, ERα is an important factor that plays essential roles in cancer development, progression, and treatment [28,29], and is considered a novel therapeutic target [30]. Furthermore, several studies have shown that the regulation of ERα through HDACs or DNA methyltransferases (DNMTs) [31][32][33] indicates the significance of the epigenetic regulation of ERα in breast cancer.…”

The role of estrogen receptor beta in breast cancer

“…However, in another study including 78 women who were postmenopausal with primary stage II to III invasive breast cancer, ERβ did not change when comparing samples from before and after endocrine treatment [45]. Since the role of ERβ in breast cancer remains unclear, the latest studies have made efforts to explore the relationship between ERβ and clinical outcome in many aspects, including the predictive value of ERβ expression [46], the ERβ to ERα ratio [45] and the DNA promoter hypermethylation of ERβ [47], especially in patients who have undergone endocrine therapy [48,49] and chemotherapy [44,50]. In general, numerous studies have verified that ERβ is an independent prognostic and/or predictive factor in breast cancer, although the conclusion is still controversial.…”

“…The relative levels of ERβ and ERα in breast cancer are related to the activities of multiple signaling pathways responsible for cell proliferation and endocrine therapy response [45,76]. A study shows that under the condition of coexpression of ERα and ERβ, HER2 expression is frequently found to be negative, whereas the Ki-67 index is upregulated, indicating an association between this special combination of biomarkers and breast cancer aggressiveness [46]. Furthermore, elevated ERβ can affect ERα expression at the transcriptional level through downregulation of basal ERα promoter activity.…”

Estrogen Receptor β Expression and Its Clinical Implication in Breast Cancers: Favorable or Unfavorable?

“…High ERβ mRNA is correlated with high Ki-67 positivity, large tumors and higher stage BCa in ERα-negative /ERβ-positive BCa [ 12 17 ]. Further, co-expression of ERβ and ERα was associated with BCa aggressiveness including higher-grade and positive nodal status, and high Ki-67 positivity [ 70 ]. Findings of high proliferative markers of Ki-67 in tumors expressing ERβ isoforms support that ERβ may drive proliferation and involved in carcinogenesis.…”