par El Khissiin, Abdelhamid 
;Journé, Fabrice ;Laïos, Ioanna;Seo, Hye-Sook ;Leclercq, Guy
Référence Steroids, 65, 12, page (903-913)
Publication Publié, 2000
;Journé, Fabrice ;Laïos, Ioanna;Seo, Hye-Sook ;Leclercq, Guy Référence Steroids, 65, 12, page (903-913)
Publication Publié, 2000
Article révisé par les pairs
| Résumé : | In MCF-7 breast cancer cells, hydroxytamoxifen (OH-Tam) up-regulates the estrogen receptor (ER) in a form unable to bind [3H]estradiol (E2). We show here that this property is not restricted to this antiestrogen. [3H]E2 binding assays (whole cell assays, DCC assays on cell extracts) and enzyme immunoassays (Abbott) performed in parallel, establish the permanent presence of such unusual ERs in the absence of any exposure of the cells to a ligand. E2 and the pure antiestrogen RU 58 668, which down-regulate ER, also decrease [3H]E2 binding. In control cells, these ERs represent about the half of the whole receptor population; they also display a tendency to stabilize within the cell nucleus. Loss of E2 binding ability appears irreversible, since we failed to label receptor accumulated under OH-Tam with [3H]E2 or [3H]tamoxifen aziridine (TAZ). Cycloheximide (CHX), which blocks E2-induced down regulation of ER, failed to stabilize [3H]E2 binding (whole cell assay) after an [3H]E2 pulse (1 h), confirming that regulation of E2 binding and peptide level are related to different regulatory mechanisms. Loss of binding ability could not be ascribed to any ER cleavage as demonstrated by Western blotting with a panel of ER antibodies raised against its various domains (67 kDa ER solely detected). We propose that loss of E2 binding ability is related to the aging process of the receptor, i.e. it is progressively converted to a form devoted to degradation after it has accomplished its physiological role. Ligands may favor (E2, RU 58 668) or impede (OH-Tam) this elimination process. (C) 2000 Elsevier Science Inc. |
