Accumulation of a non-binding form of estrogen receptor in MCF-7 cells under hydroxytamoxifen treatment
| Autor: | Nicole Legros, Guy Leclercq, Martine Piccart |
|---|---|
| Rok vydání: | 1992 |
| Předmět: |
medicine.drug_class
Endocrinology Diabetes and Metabolism Blotting Western Clinical Biochemistry Estrogen receptor Breast Neoplasms Biochemistry Cell Line Structure-Activity Relationship Endocrinology Centrifugation Density Gradient Tumor Cells Cultured medicine Humans skin and connective tissue diseases Receptor Molecular Biology Estrogen receptor beta Estradiol Chemistry Cell growth Estrogen Antagonists Cell Biology Antiestrogen In vitro Molecular Weight Blot Tamoxifen Receptors Estrogen Estrogen Molecular Medicine Female Receptors Progesterone hormones hormone substitutes and hormone antagonists |
| Zdroj: | The Journal of Steroid Biochemistry and Molecular Biology. 41:545-552 |
| ISSN: | 0960-0760 |
| DOI: | 10.1016/0960-0760(92)90381-r |
| Popis: | It is well known that MCF-7 cells, when incubated with hydroxytamoxifen (OH-Tam) loose their capacity to bind [3H]estradiol. By using Western blotting and [3H]tamoxifen aziridine labeling of KCl extracts from these cells we found that this loss in binding capacity was not associated with a disappearance of the estrogen receptor (ER) protein, an event known to occur after incubation with estradiol. Attempts to label under exchange conditions these ER molecules, which, on the basis of enzyme immunoassays appear to accumulate under OH-Tam treatment, were unsuccessful. Cell fractionation suggested that their origin is nuclear. Assessment of a few triphenylethylenic antiestrogens, as far as their inhibitory potency towards the in vitro MCF-7 cell growth is concerned, indicated a correlation between accumulation of these non-binding ER molecules and the antiestrogen antiproliferative action. However, we were unable to demonstrate absence of such an ER accumulation in two tamoxifen-resistant variants. Impaired folding of the ER protein or impaired phosphorylation of its hormone-binding domain are attractive hypotheses to account for these non-binding ER molecules. Whether these ER molecules have any physiological role, such as competition with the "normal" receptor molecules for the estrogen responsive elements on the DNA is unknown and deserves further study. |
| Databáze: | OpenAIRE |
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