PREFERENTIAL STIMULATION OF HUMAN PROGESTERONE-RECEPTOR-B EXPRESSION BY ESTROGEN IN T-47D HUMAN BREAST-CANCER CELLS

Human progesterone receptor (PR) expression is controlled by two promo ter regions giving rise to transcripts encoding PR A and B proteins. I t is unknown whether estrogen and progesterone, the major physiologica l modulators of PR expression, exert their effects equally on the PR p romoters. The aim of this study was to analyze estrogen and progestin effects on PR promoters, PR-encoding transcripts, and PR A and B prote ins in T-47D human breast cancer cells. The progestin ORG 2058 caused a prolonged decrease in transcription of the PR gene and also abrogate d estrogen stimulation of PR transcription. Estradiol (E2) treatment i ncreased the activity of the B but not the A promoter transfected into T-47D cells. ORG 2058 had no effect on the basal or E2-stimulated act ivity of either promoter. E2 caused a preferential increase in transcr ipts derived from promoter B, whereas progestins decreased the levels of all PR transcripts. E2 preferentially increased the concentration o f the PR B protein and caused a decrease in the PR A/B ratio. This dem onstration that estrogen and progestin independently control the synth esis of transcripts arising from the PR promoters and that estrogen al ters the cellular PR A/B ratio provides possible mechanisms underlying the cell and tissue specificity of PR regulation.