2020
DOI: 10.1210/endocr/bqaa224
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Genome-Wide Estrogen Receptor Activity in Breast Cancer

Abstract: The largest subtype of breast cancer is characterized by the expression and activity of the estrogen receptor alpha (ERalpha/ER). Although several effective therapies have significantly improved survival, the adaptability of cancer cells means that patients frequently stop responding or develop resistance to endocrine treatment. ER does not function in isolation and multiple associating factors have been reported to play a role in regulating the estrogen-driven transcriptional program. This review focuses on t… Show more

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Cited by 36 publications
(30 citation statements)
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“…The heatmap showing hierarchical clustering and comparing the recruitment pattern induced by E4 and E2 revealed that both estrogens induced the binding between ERα and a similar subset of coregulators (Figure 7A, Figure S5). As expected, E2 induced the recruitment of well-characterized ERα coregulators [42,45] such as the co-activators mediator complex subunit 1 (MED1), proline-, glutamic acid-and leucine-rich protein 1 (PELP1), steroid receptor coactivator (SRC) 1, SRC2, SRC3, cAMP response element-binding protein (CBP/p300), bromodomaincontaining protein 8 (BRD8) or the co-repressors ligand-dependent corepressor (LCoR) and nuclear receptor-interacting protein 1 (NRIP1/RIP140) (Figure 7B). E4 also induced the recruitment of these coregulators to ERα, although the potency of E4 was lower than that of E2.…”
Section: E4 Is Less Potent Than E2 In Inducing the Recruitment Of Co-regulators To Erα In Breast Cancer Cellssupporting
confidence: 80%
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“…The heatmap showing hierarchical clustering and comparing the recruitment pattern induced by E4 and E2 revealed that both estrogens induced the binding between ERα and a similar subset of coregulators (Figure 7A, Figure S5). As expected, E2 induced the recruitment of well-characterized ERα coregulators [42,45] such as the co-activators mediator complex subunit 1 (MED1), proline-, glutamic acid-and leucine-rich protein 1 (PELP1), steroid receptor coactivator (SRC) 1, SRC2, SRC3, cAMP response element-binding protein (CBP/p300), bromodomaincontaining protein 8 (BRD8) or the co-repressors ligand-dependent corepressor (LCoR) and nuclear receptor-interacting protein 1 (NRIP1/RIP140) (Figure 7B). E4 also induced the recruitment of these coregulators to ERα, although the potency of E4 was lower than that of E2.…”
Section: E4 Is Less Potent Than E2 In Inducing the Recruitment Of Co-regulators To Erα In Breast Cancer Cellssupporting
confidence: 80%
“…Interestingly, E4 predominantly upregulated ALX4, a tumor suppressor transcription factor downregulated in breast cancer cell lines such as MCF7 and in 70% of breast cancer from patients [48]. Finally, by evaluating the interaction between ERα and 154 coregulator motifs, which are key determinants controlling ERαmediated transcriptional regulation [42], we found that the binding of either E2 or E4 to ERα recruits a similar subset of coregulators when the E4 concentration is 50 times higher than the E2 one. Nevertheless, the slope of these binding curves indicates that E2 only needs a slight increase of concentration to reach its maximal activity, although E4-related ERα activation is more progressive.…”
Section: Discussionmentioning
confidence: 78%
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“…The PHF20 (PHF20) protein regulates p53 signaling and epigenetic regulation by chromatin regulation/histone deacetylases 25 , as does CREBBP protein a histone acetyltransferase and transcriptional coactivator 26 , findings in sync with the 9-gene set, DNA methylation, and protein datasets we analyzed. Less information is available for proteins encoded by GATAD2A , DDX17 , NUP214 although they appear to share estrogen and androgen receptor regulatory properties 27 30 .…”
Section: Discussionmentioning
confidence: 99%
“…Genome-wide ER chromatin binding patterns, called cistromes, are associated with ER-mediated transcriptional activity in endocrine-sensitive and endocrine-resistant breast cancer contexts 1 . ER chromatin binding is primarily located at distal regulatory elements and putative enhancer regions [4][5][6][7][8] .…”
Section: Mainmentioning
confidence: 99%