Two promoters in expression of estrogen receptor messenger RNA in human breast cancer

The human estrogen receptor (ER) gene has recently been shown to transcribe two types of mRNA originating from two distinct promoters in mammary tumor cell lines, which encode the same protein. However, use of the two promoters has not been addressed in human breast cancer, which reveals a heterogeneity in terms of ER expression status and clinical characteristics. In this report, we investigated which promoter is responsible for the expression of ER in human mammary tumors by a semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) analysis for discriminatory detection of the two transcripts in mammary tissues obtained from patients with breast cancer. First, the use of distinct promoters was confirmed in several mammary tumor cell lines by the present RT-PCR method. Secondly, expression levels of total ER mRNA and two types of mRNAs from the different promoters were analysed in tumor, surrounding tissue and normal tissue obtained from 12 patients with breast cancer, which showed various levels of ER protein. In tumors, levels of total ER mRNA and the mRNA transcribed from a distal promoter showed remarkable correlation to the ER protein levels with correlation coefficients 0.946 (P < 0.001) and 0.746 (P < 0.005), respectively. In contrast, mRNA from a proximal promoter showed no correlation to the ER protein levels. Our results indicate that the enhancement of the ER mRNA expression from the distal promoter plays an essential role in the mechanisms of overexpressing ER protein in human mammary tumors, implying that a tumor-specific regulation of ER expression involved use of the distal promoter.