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 promoter regions giving rise to transcripts encoding PR A and B proteins. It is unknown whether estrogen and progesterone, the major physiological modulators of PR expression, exert their effects equally on the PR promoters. The aim of this study was to analyze estrogen and progestin effects on PR promoters, PR-encoding transcripts, and PR A and B proteins in T-47D human breast cancer cells. The progestin ORG 2058 caused a prolonged decrease in transcription of the PR gene and also abrogated estrogen stimulation of PR transcription. Estradiol (E2) treatment increased 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 activity of either promoter. E2 caused a preferential increase in transcripts derived from promoter B, whereas progestins decreased the levels of all PR transcripts. E2 preferentially increased the concentration of the PR B protein and caused a decrease in the PR A/B ratio. This demonstration that estrogen and progestin independently control the synthesis of transcripts arising from the PR promoters and that estrogen alters the cellular PR A/B ratio provides possible mechanisms underlying the cell and tissue specificity of PR regulation.
Department of Medical Oncology, University of Sydney, Westmead Hospital, New South Wales, Australia.
J D
JD
Graham
S D
SD
Roman
E
E
McGowan
R L
RL
Sutherland
C L
CL
Clarke
D001943:Breast Neoplasms; D002460:Cell Line; D004347:Drug Interactions; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007700:Kinetics; D011282:Pregnenediones / Q000494:pharmacology; D045167:Progesterone Congeners / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D015347:RNA Probes; D016372:RNA, Antisense; D012333:RNA, Messenger / Q000032:analysis / Q000096:biosynthesis; D011980:Receptors, Progesterone / Q000096:biosynthesis* / Q000235:genetics; D011994:Recombinant Proteins / Q000096:biosynthesis; D014158:Transcription, Genetic / Q000187:drug effects; D014162:Transfection; D014407:Tumor Cells, Cultured
D011282:Pregnenediones; D045167:Progesterone Congeners; D015347:RNA Probes; D016372:RNA, Antisense; D012333:RNA, Messenger; D011980:Receptors, Progesterone; D011994:Recombinant Proteins; C097314:progesterone receptor B; C020175:16 alpha-ethyl-21-hydroxy-19-nor-4-pregnene-3,20-dione; D004958:Estradiol