QUANTITATIVE-ANALYSIS OF THE TRANSCRIPTIONAL START SITES OF ESTROGEN-RECEPTOR IN BREAST-CARCINOMA

Recent studies have identified an estrogen receptor (ER) promoter upst ream of the transcriptional start site originally mapped for the ER ge ne. We have examined promoter use in a number of breast carcinoma cell lines. MCF7, T47D, BT474, and MDA-MB-361 cell lines all use the PO pr omoter, whereas BT20 and ZR75-1 do not demonstrate transcription from this upstream start site. S1 nuclease analysis was used to quantitate the amount of ER mRNA originating from the two different promoters. In MCF7, one-third of the ER mRNA results from transcription originating upstream of the major ER promoter and in T47D, 12% of the message ori ginates from upstream transcription. Promoter use was analyzed in huma n mammary epithelial cells and human late proliferation endometrium. U pstream promoter use was found to be characteristic of human late prol iferation endometrium but not human mammary epithelial cells. These re sults indicated that certain breast carcinomas demonstrate ER transcri ption from a promoter not normally active in normal breast epithelium. This activation may involve a factor active in normal human endometri um.