We are analyzing https://link.springer.com/article/10.1007/s10549-010-1023-8.

Title:
Inhibition of estrogen signaling activates the NRF2 pathway in breast cancer | Breast Cancer Research and Treatment
Description:
Exposure to higher levels of estrogen produces genotoxic metabolites that can stimulate mammary tumorigenesis. Induction of NF-E2-related factor 2 (NRF2)-dependent detoxifying enzymes (e.g., NAD(P)H-quinone oxidoreductase 1 (NQO1)) is considered an important mechanism of protection against estrogen-associated carcinogenesis because they would facilitate removal of toxic estrogens. Here, we studied the impact of estrogen-receptor (ER) signaling on NRF2-dependent gene transcription. In luciferase assay experiments using the 5-flanking region of the human NQO1 gene promoter, we observe that ERα ligand-binding domain (LBD) is required for estrogen inhibition of NQO1 promoter activity in estrogen-dependent breast cancer cells. Chromatin immunoprecipitation (ChIP) assay shows that estrogen recruits ERα and a class III histone deacetylase SIRT1 at the NQO1 promoter, leading to inhibition of NQO1 transcription. Inhibition of ERα expression by the antiestrogen shikonin reverses the inhibitory effect of estrogen on NQO1 expression. As a consequence, a chemoprevention study was undertaken to monitor the impact of shikonin on DNA lesions and tumor growth. Treatment of MCF-7 breast cancer cells with shikonin inhibits estrogen-induced 8-hydroxy-2-deoxyguanosine (8-OHdG), a marker of DNA damage. NQO1 deficiency promotes estrogen-dependent tumor formation, and shikonin inhibits estrogen-dependent tumor growth in an NQO1-dependent manner in MCF-7 xenografts. These results suggest that estrogen-receptor signaling pathway has an inhibitory effect on NRF2-dependent enzymes. Moreover, shikonin reverses the inhibitory effects of estrogen on this pathway and may contribute to breast cancer prevention.
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Keywords {🔍}

article, google, scholar, pubmed, cas, cancer, estrogen, breast, nqo, inhibition, shikonin, usa, receptor, zhou, biol, tamoxifen, research, signaling, nrf, davidson, privacy, cookies, pathway, yao, brodie, kensler, carcinogenesis, gene, transcription, human, chemoprevention, dna, damage, natl, mol, content, publish, search, induction, activity, estrogendependent, expression, study, tumor, mcf, access, rogan, steroid, alpha, chem,

Topics {✒️}

antiestrogen-liganded estrogen receptor-alpha nrf2-dependent gene transcription month download article/chapter antagonist-occupied steroid receptors small-cell lung cancer nf-e2-related factor 2 erα ligand-binding domain dysfunctional keap1-nrf2 interaction estrogen-receptor signaling pathway full article pdf ligand-dependent interaction estrogen receptor alpha deoxyribonucleic acid binding privacy choices/manage cookies estrogen-induced mammary antiestrogen shikonin reverses nqo1-dependent manner estrogen receptor-beta dependent detoxifying enzymes article yao nrf2-dependent enzymes endogenous tumor initiators estrogen signaling activates kensler tw estrogen recruits erα montano mm h-quinone oxidoreductase 1 cell survival responses nqo1 promoter activity european economic area stimulate mammary tumorigenesis cavalieri el van breemen rb erbeta coactivator complex protein phosphatase 2a coactivators pgc-1beta src-1 interact functionally aromatase inhibitor letrozole mcf-7 tumors implanted tumoristatic action genotoxic mutagenic carcinogen graham jd nih p50 ca088843 conditions privacy policy estradiol-stimulated growth cancer protective genes pittsburgh cancer institute nqo1 transcription luciferase assay experiments mediate transcriptional upregulation

Questions {❓}

Kensler TW, Wakabayashi N (2010) Nrf2: friend or foe for chemoprevention?
Liehr JG (2000) Is estradiol a genotoxic mutagenic carcinogen?

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