Post-transcriptional destabilization of estrogen receptor mRNA in MCF-7 cells by 12-O-tetradecanoylphorbol-13-acetate

The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the regulation of the estrogen receptor (ER) was investigated in this study. After treatment with 100 nM TPA the concentration of receptor protein was measured using an enzyme immunoassay. By 24 h the receptor protein declined by about 80%...

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Veröffentlicht in:The Journal of biological chemistry 1991-09, Vol.266 (27), p.17809-17814
Hauptverfasser: SACEDA, M, KNABBE, C, DICKSON, R. B, LIPPMAN, M. E, BRONZERT, D, LINDSEY, R. K, GOTTARDIS, M. M, MARTIN, M. B
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container_end_page 17814
container_issue 27
container_start_page 17809
container_title The Journal of biological chemistry
container_volume 266
creator SACEDA, M
KNABBE, C
DICKSON, R. B
LIPPMAN, M. E
BRONZERT, D
LINDSEY, R. K
GOTTARDIS, M. M
MARTIN, M. B
description The effect of 12-O-tetradecanoylphorbol-13-acetate (TPA) on the regulation of the estrogen receptor (ER) was investigated in this study. After treatment with 100 nM TPA the concentration of receptor protein was measured using an enzyme immunoassay. By 24 h the receptor protein declined by about 80% from a level of approximately 236 fmol of ER/mg of protein in control cells to 50 fmol of ER/mg of protein in cells treated with TPA. Similar results were obtained with an estrogen receptor ligand binding assay. After removal of TPA, the level of ER returned to control values. 4-alpha-Phorbol, a compound related to TPA, had no effect on ER. The effects of TPA on ER expression appear to be mediated by activation of protein kinase C as H-7, an inhibitor of protein kinase C, blocks these effects. In addition to the effect on ER protein, TPA treatment also resulted in a decrease in the steady-state level of ER mRNA as determined by a RNase protection assay. The metabolic inhibitor cycloheximide was unable to prevent the TPA-induced decrease in ER mRNA. Transcription run-off experiments demonstrated that TPA had no effect on ER gene transcription. A half-life study demonstrated that TPA decreased ER mRNA half-life by a factor of 6 from approximately 4 h in control cells to 40 min in TPA-treated cells. These data suggest that the decline in ER expression is mediated by post-transcriptional destabilization of ER mRNA.
doi_str_mv 10.1016/S0021-9258(18)55199-1
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source MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; Alma/SFX Local Collection
subjects Biological and medical sciences
Cell receptors
Cell structures and functions
Cycloheximide - pharmacology
ErbB Receptors - genetics
Fundamental and applied biological sciences. Psychology
Half-Life
Hormone receptors. Growth factor receptors. Cytokine receptors. Prostaglandin receptors
Humans
Immunoenzyme Techniques
Molecular and cellular biology
Plasmids
Protein Kinase C - metabolism
Proto-Oncogene Proteins c-myc - genetics
Receptors, Estrogen - genetics
RNA Processing, Post-Transcriptional - drug effects
RNA, Messenger - genetics
RNA, Messenger - metabolism
Tetradecanoylphorbol Acetate - pharmacology
Transcription, Genetic
Tumor Cells, Cultured
title Post-transcriptional destabilization of estrogen receptor mRNA in MCF-7 cells by 12-O-tetradecanoylphorbol-13-acetate
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