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Gene expression profiles of 4-hydroxy-N-desmethyl-tamoxifen (endoxifen)- and 4-hydroxy-tamoxifen (4OHTAM)-treated human breast cancer cells determined by CDNA microarray analysis
- Source :
- Clinical Pharmacology & Therapeutics. 75:P49
- Publication Year :
- 2004
- Publisher :
- Springer Science and Business Media LLC, 2004.
-
Abstract
- Recently, we have shown that endoxifen and 4OHTAM are equipotent inhibitors of estrogen action, with respect to estrogen receptor (ER) binding, proliferation, and inhibition of pS2 and PR gene expression. Since estrogens and anti-estrogens have effects on the expression of many additional genes, we tested the effects of endoxifen and 4OHTAM on genome-wide profiling in ER-positive MCF-7 cell lines by cDNA microarray analysis using the Affymetrix HG-U133A GeneChip. Cells were treated for 24 hrs with vehicle, 17β-estradiol (E2) 10−10M, 4OHTAM 10−7M, endoxifen 10−7M, E2+4OHTAM, E2+endoxifen, and E2+4OHTAM+endoxifen. E2 treatment resulted in up- or down-regulation of ~213 genes which showed greater than 2-fold changes from the vehicle-treated group. 4OHTAM and endoxifen changed the expression of 58 and 52 genes respectively when added to the E2 treatment. Of these genes, 49 (84.5%) and 46 (88.5%) were estrogen-regulated genes. 4OHTAM and endoxifen had overlapping effects on 32 genes, but also brought about distinct patterns of gene regulation (26 vs. 20 genes were changed by only 4OHTAM or endoxifen, resp.). Among the 32 genes coregulated by both 4OHTAM and endoxifen, there was a significant correlation between the fold-effects brought about by these two drugs (R2=0.964, P
Details
- ISSN :
- 00099236
- Volume :
- 75
- Database :
- OpenAIRE
- Journal :
- Clinical Pharmacology & Therapeutics
- Accession number :
- edsair.doi...........38881b5f6908cb608b30cf62fb8084f7