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- W2107899432 abstract "Abstract Using Western blot as the major technique, we studied the effects of the three Food and Drug Administration (FDA)–approved aromatase inhibitors (AI) on aromatase protein stability in the aromatase-overexpressing breast cancer cell line MCF-7aro. We have found that exemestane treatment significantly reduces aromatase protein level. Exemestane induces aromatase degradation in a dose-responsive manner (25-200 nmol/L), and the effect can be seen in as early as 2 hours. Metabolic labeling with S35-methionine was used to determine the half-life (t1/2) of aromatase protein. In the presence of 200 nmol/L exemestane, the t1/2 of aromatase was reduced to 12.5 hours from 28.2 hours in the untreated cells. Furthermore, exemestane-induced aromatase degradation can be completely blocked by 10 μmol/L MG132, indicating that the degradation is mediated by proteasome. We also examined the effect of exemestane on aromatase mRNA level using real-time reverse transcription-PCR. No significant changes in mRNA level were detected after 8 hours of treatment with exemestane (200 nmol/L). This is the first report on the evaluation of three FDA-approved AIs on the stability of the aromatase protein. We have found that exemestane, different from letrozole and anastrozole, can destabilize the aromatase protein. (Cancer Res 2006; 66(21): 10281-6)" @default.
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- W2107899432 date "2006-11-01" @default.
- W2107899432 modified "2023-10-16" @default.
- W2107899432 title "Aromatase Destabilizer: Novel Action of Exemestane, a Food and Drug Administration–Approved Aromatase Inhibitor" @default.
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- W2107899432 doi "https://doi.org/10.1158/0008-5472.can-06-2134" @default.
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