Quantification of estrogen receptor α and β expression in sporadic breast cancer

Abstract

The recent cloning of a second estrogen receptor (ER), designated ERβ, has prompted a reevaluation of the role of ERs in breast cancer. We have developed and validated a real-time RT–PCR assay to quantify ERα and ERβ gene expression at the mRNA level in a series of 131 patients with unilateral invasive primary breast cancer. Although ERβ expression showed wide variations in tumor tissues, its range (nearly three orders of magnitude) was smaller than that of ERα (nearly four orders of magnitude), suggesting that ERβ is more tightly controlled than ERα. We observed a negative correlation between ERα and ERβ expression. ‘ERα-negative’ tumors (containing very low ERα mRNA levels) were associated with SBR histopathological grade III, RB1 underexpression and ERBB2 overexpression, confirming that ERα negativity delineates poorly differentiated tumors. The amount of ERα mRNA (but not that of ERβ mRNA) increased with age and was consequently higher in postmenopausal patients' tumors. Expression of ERα (but not that of ERβ) also correlated strongly with progesterone receptor (PR) and PS2 expression, suggesting that ERα has stronger transcriptional activity than ERβ towards genes containing an ERE (estrogen response element) in their promoters. Interestingly, we found a negative correlation between the expression of ERβ (but not ERα) and CCND1, which contains an AP1 element but not an ERE in its promoter. Taken together, these data confirm that ERα and ERβ play different roles in breast cancer, partly by mediating the transcription of various genes via different types of DNA enhancer. PR and PS2 seem to be mainly ERα-responsive genes, whereas CCND1 may be mainly ERβ-responsive. Our findings also underline the need for a reliable method, providing full range of quantitative values, to determine ERα and ERβ status in the clinical setting.