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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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Published in: | The Journal of biological chemistry 1991-09, Vol.266 (27), p.17809-17814 |
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Main Authors: | , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | 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. |
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ISSN: | 0021-9258 1083-351X |
DOI: | 10.1016/S0021-9258(18)55199-1 |