Jd. Graham et al., PREFERENTIAL STIMULATION OF HUMAN PROGESTERONE-RECEPTOR-B EXPRESSION BY ESTROGEN IN T-47D HUMAN BREAST-CANCER CELLS, The Journal of biological chemistry, 270(51), 1995, pp. 30693-30700
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.