2 PROMOTERS IN EXPRESSION OF ESTROGEN-RECEPTOR MESSENGER-RNA IN HUMANBREAST-CANCER

The human estrogen receptor (ER) gene has recently been shown to trans cribe two types of mRNA originating from two distinct promoters in mam mary 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 re sponsible for the expression of ER in human mammary tumors by a semi-q uantitative reverse transcription-polymerase chain reaction CRT-PCR) a nalysis 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 b y the present RT-PCR method, Secondly, expression levels of total ER m RNA and two types of mRNAs from the different promoters were analysed in tumor, surrounding tissue and normal tissue obtained from 12 patien ts with breast cancer, which showed various levels of ER protein, In t umors, levels of total ER mRNA and the mRNA transcribed from a distal promoter showed remarkable correlation;to the ER protein levels with c orrelation coefficients 0.946 (P < 0.001) and 0.746 (P < 0.005), respe ctively, In contrast, mRNA from a proximal promoter showed no correlat ion to the ER protein levels, Our results indicate that the enhancemen t of the ER mRNA expression from the distal promoter plays an essentia l role in the mechanisms of overexpressing ER protein in human mammary tumors, implying that a tumor-specific regulation of ER expression in volved use of the distal promoter.