Regulation of the estrogen receptor in MCF-7 cells by estradiol.
The role of estradiol in the regulation of its cognate receptor in MCF-7 cells was investigated in this study. After treatment with 10(-9) M estradiol, the level of receptor protein was measured using an enzymeimmunoassay. By 6 h, the receptor protein declined by about 60% from a level of approximately 3.6 to 1.2 fmol/micrograms DNA. The level of receptor remained suppressed for 24-48 h. Similar results were obtained with an estrogen receptor (ER) binding assay. The steady state level of ER mRNA was determined by an RNase protection assay. Estrogen treatment resulted in a maximum suppression of mRNA by 6 h. Receptor mRNA remained depressed for 48 h. Transcription run on experiments demonstrated a transient decrease of about 90% in ER transcription after 1 h. By 3-6 h transcription increased approximately 2-fold and remained elevated for at least 48 h. These data suggest that estrogen down-regulates ER mRNA by inhibition of ER gene transcription at early times and by a posttranscriptional effect on receptor mRNA at later times.
Saceda
M
M
Medical Breast Cancer Section, National Cancer Institute, Bethesda, Maryland 20892.
Lippman
M E
ME
Chambon
P
P
Lindsey
R L
RL
Ponglikitmongkol
M
M
Puente
M
M
Martin
M B
MB
D001943:Breast Neoplasms / Q000378:metabolism; D002460:Cell Line; D004958:Estradiol / Q000494:pharmacology*; D005260:Female; D006801:Humans; D012333:RNA, Messenger / Q000032:analysis / Q000187:drug effects; D011960:Receptors, Estrogen / Q000187:drug effects* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure
D012333:RNA, Messenger; D011960:Receptors, Estrogen; D004958:Estradiol