28 results found
Periyasamy M, Singh A, Gemma C, et al., 2020, Induction of APOBEC3B expression by chemotherapy drugs is mediated by DNA-PK directed activation of NF-κB, Oncogene, Vol: 15 December 2020, Pages: 1077-1090, ISSN: 0950-9232
The mutagenic APOBEC3B (A3B) cytosine deaminase is frequently over-expressed in cancer and promotes tumour heterogeneity and therapy resistance. Hence, understanding the mechanisms that underlie A3B over-expression is important, especially for developing therapeutic approaches to reducing A3B levels, and consequently limiting cancer mutagenesis. We previously demonstrated that A3B is repressed by p53 and p53 mutation increases A3B expression. Here, we investigate A3B expression upon treatment with chemotherapeutic drugs that activate p53, including 5-fluorouracil, etoposide and cisplatin. Contrary to expectation, these drugs induced A3B expression and concomitant cellular cytosine deaminase activity. A3B induction was p53-independent, as chemotherapy drugs stimulated A3B expression in p53 mutant cells. These drugs commonly activate ATM, ATR and DNA-PKcs. Using specific inhibitors and gene knockdowns, we show that activation of DNA-PKcs and ATM by chemotherapeutic drugs promotes NF-kB activity, with consequent recruitment of NF-kB to the A3B gene promoter to drive A3B expression. Further, we find that A3B knockdown re-sensitises resistant cells to cisplatin, and A3B knockout enhances sensitivity to chemotherapy drugs. Our data highlight a role for A3B in resistance to chemotherapy and indicate that stimulation of A3B expression by activation of DNA repair and NF-kB pathways could promote cancer mutations and expedite chemoresistance.
Flach KD, Periyasamy M, Jadhav A, et al., 2020, Endonuclease FEN1 coregulates ER alpha activity and provides a novel drug interface in tamoxifen-resistant breast cancer, Cancer Research, Vol: 80, Pages: 1914-1926, ISSN: 0008-5472
Estrogen receptor α (ERα) is a key transcriptional regulator in the majority of breast cancers. ERα-positive patients are frequently treated with tamoxifen, but resistance is common. In this study, we refined a previously identified 111-gene outcome prediction-classifier, revealing FEN1 as the strongest determining factor in ERα-positive patient prognostication. FEN1 levels were predictive of outcome in tamoxifen-treated patients, and FEN1 played a causal role in ERα-driven cell growth. FEN1 impacted the transcriptional activity of ERα by facilitating coactivator recruitment to the ERα transcriptional complex. FEN1 blockade induced proteasome-mediated degradation of activated ERα, resulting in loss of ERα-driven gene expression and eradicated tumor cell proliferation. Finally, a high-throughput 465,195 compound screen identified a novel FEN1 inhibitor, which effectively blocked ERα function and inhibited proliferation of tamoxifen-resistant cell lines as well as ex vivo–cultured ERα-positive breast tumors. Collectively, these results provide therapeutic proof of principle for FEN1 blockade in tamoxifen-resistant breast cancer.
Nguyen VTM, Barozzi I, Faronato M, et al., 2019, Author Correction: Differential epigenetic reprogramming in response to specific endocrine therapies promotes cholesterol biosynthesis and cellular invasion, Nature Communications, Vol: 10, ISSN: 2041-1723
Ali S, Patel H, Periyasamy M, et al., 2018, ICEC0942, an orally bioavailable selective inhibitor of CDK7 for cancer treatment, Molecular Cancer Therapeutics, ISSN: 1535-7163
Recent reports indicate that some cancer types are especially sensitive to transcription inhibition, suggesting that targeting the transcriptional machinery provides new approaches to cancer treatment. Cyclin-dependent kinase (CDK)7 is necessary for transcription, and acts by phosphorylating the C-terminal domain (CTD) of RNA polymerase II (PolII) to enable transcription initiation. CDK7 additionally regulates the activities of a number of transcription factors, including Estrogen receptor-α (ER). Here we describe a new, orally bioavailable CDK7 inhibitor, ICEC0942. It selectively inhibits CDK7, with an IC50 of 40nM; IC50 values for CDK1, CDK2, CDK5 and CDK9 were 45-, 15-, 230- and 30-fold higher. In vitro studies show that a wide range of cancer types are sensitive to CDK7 inhibition with GI50 values ranging between 0.2-0.3 µM. In xenografts of both breast and colorectal cancers, the drug has substantial anti-tumor effects. Additionally, combination therapy with tamoxifen showed complete growth arrest of ER-positive tumor xenografts. Our findings reveal that CDK7 inhibition provides a new approach, especially for ER-positive breast cancer and identify ICEC0942 as a prototype drug with potential utility as a single agent or in combination with hormone therapies for breast cancer. ICEC0942 may also be effective in other cancers that display characteristics of transcription factor addiction, such as acute leukaemia, and small-cell lung cancer.
Periyasamy M, Singh A, Gemma C, et al., 2017, p53 controls expression of the DNA deaminase APOBEC3B to limit its potential mutagenic activity in cancer cells, Nucleic Acids Research, Vol: 45, Pages: 11056-11069, ISSN: 1362-4962
Cancer genome sequencing has implicated the cytosine deaminase activity of apolipoprotein B mRNA editing enzyme catalytic polypeptide-like (APOBEC) genes as an important source of mutations in diverse cancers, with APOBEC3B (A3B) expression especially correlated with such cancer mutations. To better understand the processes directing A3B over-expression in cancer, and possible therapeutic avenues for targeting A3B, we have investigated the regulation of A3B gene expression. Here, we show that A3B expression is inversely related to p53 status in different cancer types and demonstrate that this is due to a direct and pivotal role for p53 in repressing A3B expression. This occurs through the induction of p21 (CDKN1A) and the recruitment of the repressive DREAM complex to the A3B gene promoter, such that loss of p53 through mutation, or human papilloma virus-mediated inhibition, prevents recruitment of the complex, thereby causing elevated A3B expression and cytosine deaminase activity in cancer cells. As p53 is frequently mutated in cancer, our findings provide a mechanism by which p53 loss can promote cancer mutagenesis.
Harrod A, Fulton J, Nguyen VTM, et al., 2016, Genomic modelling of the ESR1 Y537S mutation for evaluating function and new therapeutic approaches for metastatic breast cancer, Oncogene, Vol: 36, Pages: 2286-2296, ISSN: 1476-5594
Drugs that inhibit estrogen receptor-α (ER) activity have been highlysuccessful in treating and reducing breast cancer progression in ER-positivedisease. However, resistance to these therapies presents a major clinicalproblem. Recent genetic studies have shown that mutations in the ER geneare found in >20% of tumours that progress on endocrine therapies.Remarkably, the great majority of these mutations localise to just a few aminoacids within or near the critical helix 12 region of the ER hormone bindingdomain, where they are likely to be single allele mutations. Understandinghow these mutations impact on ER function is a prerequiste for identifyingmethods to treat breast cancer patients featuring such mutations. Towardsthis end, we used CRISPR-Cas9 genome editing to make a single alleleknockin of the most commonly mutated amino acid residue, tyrosine 537, inthe estrogen-responsive MCF7 breast cancer cell line. Genomic analysesusing RNA-seq and ER ChIP-seq demonstrated that the Y537S mutationpromotes constitutive ER activity globally, resulting in estrogen-independentgrowth. MCF7-Y537S cells were resistant to the anti-estrogen tamoxifen andfulvestrant. Further, we show that the basal transcription factor TFIIH isconstitutively recruited by ER-Y537S, resulting in ligand-independentphosphorylation of Serine 118 (Ser118) by the TFIIH kinase, CDK7. TheCDK7 inhibitor, THZ1 prevented Ser118 phosphorylation and inhibited growthof MCF7-Y537S cells. These studies confirm the functional importance of ERmutations in endocrine resistance, demonstrate the utility of knockinmutational models for investigating alternative therapeutic approaches andhighlight CDK7 inhibition as a potential therapy for endocrine resistant breastcancer mediated by ER mutations.
Ali S, Patel H, Periyasamy M, et al., 2016, ICEC0942, an orally bioavailable selective inhibitor of CDK7 for breast cancer, UK Breast Cancer Research Symposium, Publisher: Springer Verlag, Pages: 195-195, ISSN: 0167-6806
Fulton J, Harrod A, Van N, et al., 2016, Use of CRISPR-Cas9-mediated knockin mutagenesis of ESR1 mutations in metastatic breast cancer allow functional analysis and evaluation of treatment options, UK Breast Cancer Research Symposium, Publisher: SPRINGER, Pages: 193-193, ISSN: 0167-6806
Periyasamy M, Nguyen VTM, Patel H, et al., 2016, Cytidine deamination activity of APOBEC3B regulates estrogen receptor function in breast cancer, UK Breast Cancer Research Symposium, Publisher: Springer Verlag (Germany), Pages: 197-197, ISSN: 1573-7217
Patel H, Abduljabbar R, Lai CF, et al., 2016, CDK7, cyclin H and MAT1 is elevated in breast cancer and is prognostic in estrogen receptor- positive breast cancer, Clinical Cancer Research, Vol: 22, Pages: 5929-5938, ISSN: 1557-3265
PURPOSE: CDK-activation kinase (CAK) is required for the regulation of the cell-cycle and is a trimeric complex consisting of Cyclin Dependent Kinase 7 (CDK7), Cyclin H and the accessory protein, MAT1. CDK7 also plays a critical role in regulating transcription, primarily by phosphorylating RNA polymerase II, as well as transcription factors such as estrogen receptor-alpha(ERalpha).). Deregulation of cell cycle and transcriptional control is aare general featurefeatures of cancertumor cells, highlighting the potential for the use of CDK7 inhibitors as novel cancer therapeutics in cancer. EXPERIMENTAL DESIGN: mRNA and protein expression of CDK7 and its essential co-factors cyclinH and MAT1, were evaluated in breast cancer samples to determine if their levels are altered in cancer. Immunohistochemical staining of >900 breast cancers was used to determine the association with clinicopathological features and patient outcome. RESULTS: We show that expression of CDK7, cyclinH and MAT1 are all closely linked at the mRNA and protein level and their expression is elevated in breast cancer compared with the normal breast tissue. Intriguingly, CDK7 expression was inversely proportional to tumour grade and size and outcome analysis showed an association between CAK levels and better outcome. Moreover, CDK7 expression was positively associated with ERalpha expression and in particular with phosphorylation of ERalpha at serine 118, a site important for ERalpha transcriptional activity. CONCLUSIONS: Expression of components of the CAK complex, CDK7, MAT1 and Cyclin H are elevated in breast cancer and correlates with ERalpha.. Like ERalpha, CDK7 expression is inversely proportional to poor prognostic factors and survival.
Mollet IG, Patel D, Govani FS, et al., 2016, Low Dose Iron Treatments Induce a DNA Damage Response in Human Endothelial Cells within Minutes, PLOS One, Vol: 11, ISSN: 1932-6203
BackgroundSpontaneous reports from patients able to report vascular sequelae in real time, and recognitionthat serum non transferrin bound iron may reach or exceed 10μmol/L in the bloodstream after iron tablets or infusions, led us to hypothesize that conventional iron treatmentsmay provoke acute vascular injury. This prompted us to examine whether a phenotypecould be observed in normal human endothelial cells treated with low dose iron.MethodologyConfluent primary human endothelial cells (EC) were treated with filter-sterilized iron (II) citrateor fresh media for RNA sequencing and validation studies. RNA transcript profiles wereevaluated using directional RNA sequencing with no pre-specification of target sequences.Alignments were counted for exons and junctions of the gene strand only, blinded to treatmenttypes.Principal FindingsRapid changes in RNA transcript profiles were observed in endothelial cells treated with10μmol/L iron (II) citrate, compared to media-treated cells. Clustering for Gene Ontology(GO) performed on all differentially expressed genes revealed significant differences in biologicalprocess terms between iron and media-treated EC, whereas 10 sets of an equivalentnumber of randomly selected genes from the respective EC gene datasets showed no significantdifferences in any GO terms. After 1 hour, differentially expressed genes clusteredto vesicle mediated transport, protein catabolism, and cell cycle (Benjamini p = 0.0016,0.0024 and 0.0032 respectively), and by 6 hours, to cellular response to DNA damage stimulusmost significantly through DNA repair genes FANCG, BLM, and H2AFX. Comet assays demonstrated that 10μM iron treatment elicited DNA damage within 1 hour. This wasaccompanied by a brisk DNA damage response pulse, as ascertained by the developmentof DNA damage response (DDR) foci, and p53 stabilization.SignificanceThese data suggest that low dose iron treatments are sufficient to modify the vascular endothelium,and induce a DNA damage
Nguyen VTM, Barozzi I, Faronato M, et al., 2015, Differential epigenetic reprogramming in response to specific endocrine therapies promotes cholesterol biosynthesis and cellular invasion, Nature Communications, Vol: 6, Pages: 1-15, ISSN: 2041-1723
Endocrine therapies target the activation of the oestrogen receptor alpha (ERa) via distinctmechanisms, but it is not clear whether breast cancer cells can adapt to treatment usingdrug-specific mechanisms. Here we demonstrate that resistance emerges via drug-specificepigenetic reprogramming. Resistant cells display a spectrum of phenotypical changes withinvasive phenotypes evolving in lines resistant to the aromatase inhibitor (AI). Orthogonalgenomics analysis of reprogrammed regulatory regions identifies individual drug-inducedepigenetic states involving large topologically associating domains (TADs) and the activationof super-enhancers. AI-resistant cells activate endogenous cholesterol biosynthesis (CB)through stable epigenetic activation in vitro and in vivo. Mechanistically, CB sparks theconstitutive activation of oestrogen receptors alpha (ERa) in AI-resistant cells, partly via thebiosynthesis of 27-hydroxycholesterol. By targeting CB using statins, ERa binding is reducedand cell invasion is prevented. Epigenomic-led stratification can predict resistance to AI in asubset of ERa-positive patients.
Periyasamy M, Patel H, Lai C-F, et al., 2015, APOBEC3B mediated cytidine deamination is required for estrogen receptor action in breast cancer, Cell Reports, Vol: 13, Pages: 108-121, ISSN: 2211-1247
Estrogen receptor α (ERα) is the key transcriptional driver in a large proportion of breast cancers. We report that APOBEC3B (A3B) is required for regulation of gene expression by ER and acts by causing C-to-U deamination at ER binding regions. We show that these C-to-U changes lead to the generation of DNA strand breaks through activation of base excision repair (BER) and to repair by non-homologous end-joining (NHEJ) pathways. We provide evidence that transient cytidine deamination by A3B aids chromatin modification and remodelling at the regulatory regions of ER target genes that promotes their expression. A3B expression is associated with poor patient survival in ER+ breast cancer, reinforcing the physiological significance of A3B for ER action.
Kramer H, Lai C, Dattani H, et al., 2015, LRH-1 drives colon cancer cell growth by repressing the expression of the CDKN1A gene in a p53-dependent manner, Nucleic Acids Research, Vol: 44, Pages: 582-594, ISSN: 1362-4962
Liver receptor homologue 1 (LRH-1) is an orphan nuclearreceptor that has been implicated in the progressionof breast, pancreatic and colorectal cancer(CRC). To determine mechanisms underlying growthpromotion by LRH-1 in CRC, we undertook global expressionprofiling following siRNA-mediated LRH-1knockdown in HCT116 cells, which require LRH-1 forgrowth and in HT29 cells, in which LRH-1 does notregulate growth. Interestingly, expression of the cellcycle inhibitor p21 (CDKN1A) was regulated by LRH-1 in HCT116 cells. p21 regulation was not observedin HT29 cells, where p53 is mutated. p53 dependencefor the regulation of p21 by LRH-1 was confirmed byp53 knockdown with siRNA, while LRH-1-regulationof p21 was not evident in HCT116 cells where p53 hadbeen deleted. We demonstrate that LRH-1-mediatedp21 regulation in HCT116 cells does not involve alteredp53 protein or phosphorylation, and we showthat LRH-1 inhibits p53 recruitment to the p21 promoter,likely through a mechanism involving chromatinremodelling. Our study suggests an importantrole for LRH-1 in the growth of CRC cells that retainwild-type p53.
Lin M-L, Patel H, Remenyi J, et al., 2015, Expression profiling of nuclear receptors in breast cancer identifies TLX as a mediator of growth and invasion in triple-negative breast cancer, Oncotarget, Vol: 6, Pages: 21685-21703, ISSN: 1949-2553
he Nuclear Receptor (NR) superfamily of transcription factors comprises 48 members, several of which have been implicated in breast cancer. Most important is estrogen receptor-α (ERα), which is a key therapeutic target. ERα action is facilitated by co-operativity with other NR and there is evidence that ERα function may be recapitulated by other NRs in ERα-negative breast cancer. In order to examine the inter-relationships between nuclear receptors, and to obtain evidence for previously unsuspected roles for any NRs, we undertook quantitative RT-PCR and bioinformatics analysis to examine their expression in breast cancer. While most NRs were expressed, bioinformatic analyses differentiated tumours into distinct prognostic groups that were validated by analyzing public microarray data sets. Although ERα and progesterone receptor were dominant in distinguishing prognostic groups, other NR strengthened these groups. Clustering analysis identified several family members with potential importance in breast cancer. Specifically, RORγ is identified as being co-expressed with ERα, whilst several NRs are preferentially expressed in ERα-negative disease, with TLX expression being prognostic in this subtype. Functional studies demonstrated the importance of TLX in regulating growth and invasion in ERα-negative breast cancer cells.
Stebbing J, Zhang H, Xu Y, et al., 2015, KSR1 regulates BRCA1 degradation and inhibits breast cancer growth, ONCOGENE, Vol: 34, Pages: 2103-2114, ISSN: 0950-9232
Pellegrino L, Stebbing J, Braga VM, et al., 2013, miR-23b regulates cytoskeletal remodeling, motility and metastasis by directly targeting multiple transcripts, Nucleic Acids Research, Vol: 41, Pages: 5400-5412, ISSN: 1362-4962
Uncontrolled cell proliferation and cytoskeletal remodeling are responsible for tumor development and ultimately metastasis. A number of studies have implicated microRNAs in the regulation of cancer cell invasion and migration. Here, we show that miR-23b regulates focal adhesion, cell spreading, cell-cell junctions and the formation of lamellipodia in breast cancer (BC), implicating a central role for it in cytoskeletal dynamics. Inhibition of miR-23b, using a specific sponge construct, leads to an increase of cell migration and metastatic spread in vivo, indicating it as a metastatic suppressor microRNA. Clinically, low miR-23b expression correlates with the development of metastases in BC patients. Mechanistically, miR-23b is able to directly inhibit a number of genes implicated in cytoskeletal remodeling in BC cells. Through intracellular signal transduction, growth factors activate the transcription factor AP-1, and we show that this in turn reduces miR-23b levels by direct binding to its promoter, releasing the pro-invasive genes from translational inhibition. In aggregate, miR-23b expression invokes a sophisticated interaction network that co-ordinates a wide range of cellular responses required to alter the cytoskeleton during cancer cell motility.
Zhang H, Lombardo Y, Filipovic A, et al., 2012, KSR1 is involved in functional interaction between p53 and BRCA1 and is an independent predictor of overall survival in breast cancer, CANCER RESEARCH, Vol: 72, ISSN: 0008-5472
Lombardo Y, Filipovic A, Molyneux G, et al., 2012, Nicastrin regulates breast cancer stem cell properties and tumor growth in vitro and in vivo, PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, Vol: 109, Pages: 16558-16563, ISSN: 0027-8424
Tolhurst RS, Thomas RS, Kyle FJ, et al., 2011, Transient over-expression of estrogen receptor-α in breast cancer cells promotes cell survival and estrogen-independent growth, BREAST CANCER RESEARCH AND TREATMENT, Vol: 128, Pages: 357-368, ISSN: 0167-6806
Thiruchelvam PTR, Lai C-F, Hua H, et al., 2011, The liver receptor homolog-1 regulates estrogen receptor expression in breast cancer cells, BREAST CANCER RESEARCH AND TREATMENT, Vol: 127, Pages: 385-396, ISSN: 0167-6806
Heathcote DA, Patel H, Kroll SH, et al., 2010, A novel pyrazolo[1,5-a]pyrimidine is a potent inhibitor of cyclin-dependent protein kinases 1, 2, and 9, which demonstrates antitumor effects in human tumor xenografts following oral administration, J Med Chem, Vol: 53, Pages: 8508-8522
Cyclin-dependent protein kinases (CDKs) are central to the appropriate regulation of cell proliferation, apoptosis, and gene expression. Abnormalities in CDK activity and regulation are common features of cancer, making CDK family members attractive targets for the development of anticancer drugs. Here, we report the identification of a pyrazolo[1,5-a]pyrimidine derived compound, 4k (BS-194), as a selective and potent CDK inhibitor, which inhibits CDK2, CDK1, CDK5, CDK7, and CDK9 (IC= 3, 30, 30, 250, and 90 nmol/L, respectively). Cell-based studies showed inhibition of the phosphorylation of CDK substrates, Rb and the RNA polymerase II C-terminal domain, down-regulation of cyclins A, E, and D1, and cell cycle block in the S and G/M phases. Consistent with these findings, 4k demonstrated potent antiproliferative activity in 60 cancer cell lines tested (mean GI= 280 nmol/L). Pharmacokinetic studies showed that 4k is orally bioavailable, with an elimination half-life of 178 min following oral dosing in mice. When administered at a concentration of 25 mg/kg orally, 4k inhibited human tumor xenografts and suppressed CDK substrate phosphorylation. These findings identify 4k as a novel, potent CDK selective inhibitor with potential for oral delivery in cancer patients.
WORTHAM NC, AHAMED E, NICHOL SM, et al., 2009, The DEAD-box protein p72 regulates ERα-/oestrogen-dependent transcription and cell growth, and is associated with improved survival in ERα-positive breast cancer, Oncogene, Vol: 28, Pages: 4053-4064, ISSN: 1476-5594
The DEAD-box RNA helicases p68 (DDX5) and p72 (DDX17) have been shown to act as transcriptional co-activators for a diverse range of transcription factors, including oestrogen receptor-α (ERα). Here, we show that, although both proteins interact with and co-activate ERα in reporter gene assays, small interfering RNA-mediated knockdown of p72, but not p68, results in a significant inhibition of oestrogen-dependent transcription of endogenous ERα-responsive genes and oestrogen-dependent growth of MCF-7 and ZR75-1 breast cancer cells. Furthermore, immunohistochemical staining of ERα-positive primary breast cancers for p68 and p72 indicate that p72 expression is associated with an increased period of relapse-free and overall survival (P=0.006 and 0.016, respectively), as well as being inversely associated with Her2 expression (P=0.008). Conversely, p68 shows no association with relapse-free period, or overall survival, but it is associated with an increased expression of Her2 (P=0.001), AIB-1 (P<0.001) and higher tumour grade (P=0.044). Our data thus highlight a crucial role for p72 in ERα co-activation and oestrogen-dependent cell growth and provide evidence in support of distinct but important roles for both p68 and p72 in regulating ERα activity in breast cancer.
Ali S, Heathcote DA, Kroll SHB, et al., 2009, The Development of a Selective Cyclin-Dependent Kinase Inhibitor That Shows Antitumor Activity, CANCER RESEARCH, Vol: 69, Pages: 6208-6215, ISSN: 0008-5472
Periyasamy M, Thomas R, Tolhurst R, et al., 2009, Investigation of the regulation of DNA methylation by the estrogen receptor, CANCER RESEARCH, Vol: 69, ISSN: 0008-5472
Coombes R, Cheiper, Jogalekar AS, et al., 2009, The development of a selective CDK7 inhibitor with anti-tumor activity, CANCER RESEARCH, Vol: 69, ISSN: 0008-5472
Ali S, Periyasamy M, Lopez-Garcia J, et al., 2008, ZNF366 is a novel corepressor for estrogen receptor alpha that mediates its effects through interaction with CtBP, Breast Cancer Research Meeting, Publisher: BIOMED CENTRAL LTD, Pages: S7-S7, ISSN: 1465-5411
Lopez-Garcia J, Periyasamy M, Thomas RS, et al., 2006, ZNF366 is an estrogen receptor corepressor that acts through CtBP and histone deacetylases, Nucleic Acids Research, Vol: 34, Pages: 6126-6136, ISSN: 1362-4962
The regulation of gene expression by estrogen receptor-α (ERα) requires the coordinated and temporal recruitment of diverse sets of transcriptional co-regulator complexes, which mediate nucleosome remodelling and histone modification. Using ERα as bait in a yeast two-hybrid screen, we have identified a novel ERα-interacting protein, ZNF366, which is a potent corepressor of ERα activity. The interaction between ZNF366 and ERα has been confirmed in vitro and in vivo, and is mediated by the zinc finger domains of the two proteins. Further, we show that ZNF366 acts as a corepressor by interacting with other known ERα corepressors, namely RIP140 and CtBP, to inhibit expression of estrogen-responsive genes in vivo. Together, our results indicate that ZNF366 may play an important role in regulating the expression of genes in response to estrogen.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.