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- W2147096476 abstract "We studied the effects of 2-methoxyestradiol (2-ME 2 ) and 16α-hydroxyestrone (16α-OHE 1 ), two metabolites of estradiol (E 2 ), on DNA synthesis, cell cycle progression and cyclin D1 protein levels in estrogen receptor-positive MCF-7 cells. E 2 and 16α-OHE 1 stimulated DNA synthesis, and 2-ME 2 inhibited the stimulatory effects of these agents. E 2 and 16α-OHE 1 stimulated the progression of cells from G 1 to S phase and this effect was attenuated by 2-ME 2 . Western blot analysis showed that E 2 and 16α-OHE 1 increased cyclin D1 protein level by about fourfold compared with control. 2-ME 2 had no significant effect on cyclin D1; however, it prevented the accumulation of cyclin D1 in the presence of E 2 and 16α-OHE 1 . Cells transfected with a cyclin D1 reporter gene and treated with E 2 or 16α-OHE 1 showed 7- and 9.5-fold increase respectively in promoter activity compared with control. This activity was significantly inhibited by 2-ME 2 . Cyclin D1 transactivation was mediated by the cAMP response element (CRE) region, which binds activating transcription factor 2 (ATF-2). DNA affinity assay showed 2.5- and 3.5-fold increases in ATF-2 binding to CRE in the presence of E 2 and 16α-OHE 1 respectively. The binding of ATF-2 was inhibited by the presence of 2-ME 2 . These results show that 2-ME 2 can downregulate cyclin D1 and thereby cell cycle progression by a mechanism involving the disruption of ATF-2 binding to cyclin D1 promoter." @default.
- W2147096476 created "2016-06-24" @default.
- W2147096476 creator A5016235708 @default.
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- W2147096476 creator A5039355847 @default.
- W2147096476 creator A5060086982 @default.
- W2147096476 date "2005-02-01" @default.
- W2147096476 modified "2023-10-14" @default.
- W2147096476 title "Differential effects of 16α-hydroxyestrone and 2-methoxyestradiol on cyclin D1 involving the transcription factor ATF-2 in MCF-7 breast cancer cells" @default.
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