Abstract:
PURPOSE:Although tamoxifen remains the frontline treatment for ERα-positive breast cancers, resistance to this drug limits its clinical efficacy. Most tamoxifen-resistant patients retain ERα expression which may support growth and progression of breast cancers. Therefore, we investigated epigenetic regulation of ERα that may provide a rationale for targeting ERα in these patients. METHODS:Expression levels of the mixed-lineage leukemia (MLL) family of proteins in tamoxifen-resistant breast cancer cells and publicly available breast cancer patient data sets were analyzed. Histone methylation levels in ERα promoter regions were assessed using chromatin immunoprecipitation. Expression levels of ERα and its target gene were analyzed using western blotting and real-time qPCR. Cell-cycle was analyzed by flow cytometry. RESULTS:The expression of MLL3 and SET-domain-containing 1A (SET1A) were increased in tamoxifen-resistant breast cancers. An MLL3 chromatin immunoprecipitation-sequencing data analysis and chromatin immunoprecipitation experiments for MLL3 and SET1A suggested that these proteins bound to enhancer or intron regions of the ESR1 gene and regulated histone H3K4 methylation status. Depletion of MLL3 or SET1A downregulated the expression level of ERα and inhibited the growth of tamoxifen-resistant breast cancer cells. Additional treatment with fulvestrant resulted in a synergistic reduction of ERα levels and the growth of the cells. CONCLUSIONS:The enhanced expression of MLL3 and SET1A in tamoxifen-resistant breast cancer cells supported the ERα-dependent growth of these cells by increasing ERα expression. Our results suggest that targeting these histone methyltransferases might provide an attractive strategy to overcome endocrine resistance.
journal_name
Breast Cancer Res Treatjournal_title
Breast cancer research and treatmentauthors
Kim SS,Lee MH,Lee MOdoi
10.1007/s10549-019-05517-0subject
Has Abstractpub_date
2020-02-01 00:00:00pages
45-54issue
1eissn
0167-6806issn
1573-7217pii
10.1007/s10549-019-05517-0journal_volume
180pub_type
杂志文章abstract::Treatment decisions in oncology are based on a balance between the efficacy of therapy and its side effects. Patients with metastases and patients with a limited prognosis are a particular challenge, since communication about the disease situation and the expected therapeutic benefit is difficult not only for patients...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-013-2557-3
更新日期:2013-06-01 00:00:00
abstract::BRCA1 protein is normally expressed in the nuclei of breast epithelial cells and functions as a negative regulator of the cell cycle. Mutations of BRCA1 gene have been associated with familial breast carcinomas. Although somatic mutations have not been demonstrated in sporadic breast carcinomas, loss of nuclear expres...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1013317909431
更新日期:2002-01-01 00:00:00
abstract::Published data on the association between Xeroderma Pigmentosum complementation group D (XPD) Lys751Gln polymorphism and breast cancer risk are inconclusive. To derive a more precise estimation of the relationship, a meta-analysis was performed. Crude ORs with 95% CIs were used to assess the strength of association be...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析
doi:10.1007/s10549-010-0813-3
更新日期:2010-11-01 00:00:00
abstract:OBJECTIVES:To determine any changes in usage of axillary dissection over time from 1983 to 1993, and to characterize those patients who do not receive axillary node dissection. METHODS:A total of 129,946 female patients receiving cancer-directed surgery for early stage breast cancer, who were identified from the SEER ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1006170811237
更新日期:1999-01-01 00:00:00
abstract::In breast cancer, the survival rate strongly depends on the number of lymph nodes involved. A drug with a specific inhibitory activity on lymph node and organ metastases would therefore be a candidate for adjuvant therapy after surgery. Prostacyclin and its stable analogues have been shown to interfere with certain st...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/BF01803791
更新日期:1996-01-01 00:00:00
abstract::To assess the impact of patient-provider communication on adherence to tamoxifen (TAM) and aromatase inhibitors (AIs) 36 months after breast cancer (BC) diagnosis in a low-income population of women. California statewide surveys were conducted among 921 low-income women with BC at 6, 18, and 36 months after BC diagnos...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-012-2387-8
更新日期:2013-02-01 00:00:00
abstract:BACKGROUND:Central nervous system (CNS) relapse is increasing in breast cancer. This increase may reflect altered failure patterns from adjuvant therapy, more effective systemic therapy with improved control in non-CNS sites, or a resistant breast cancer subtype. METHODS:To determine the factors associated with clinic...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-004-0999-3
更新日期:2004-12-01 00:00:00
abstract::Lapatinib and capecitabine combination therapy is effective in trastuzumab-resistant human epidermal growth factor receptor 2 (HER2)-positive breast cancer. We investigated the biomarkers from serum of patients receiving lapatinib and capecitabine Patients received lapatinib 1,250 mg once daily and capecitabine 2,000 ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究
doi:10.1007/s10549-010-1200-9
更新日期:2011-01-01 00:00:00
abstract::We calculated hazard rates for recurrence in patients with primary breast cancer (stage I, II; no adjuvant therapy). Previous publications have indicated a peak in hazard rates for recurrence (or death) at approximately 2-3 years after diagnosis of primary breast cancer. However, there have been conflicting reports co...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-004-1722-0
更新日期:2005-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-017-4470-7
更新日期:2018-01-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 共识发展会议,杂志文章,评审
doi:10.1007/s10549-019-05132-z
更新日期:2019-04-01 00:00:00
abstract::The epidermal growth factor (EGF) is one of several growth factors involved in normal breast epithelial development and tumor proliferation. EGF and EGF-like peptide TGF alpha bind and activate the same membrane receptor protein. This receptor (EGF-R) has been recently studied in breast tumor biopsies and its detectab...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/BF01834623
更新日期:1992-03-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/s10549-009-0429-7
更新日期:2009-08-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1017919507109
更新日期:2001-07-01 00:00:00
abstract::Transgender (TG) persons often receive, or self-treat, with cross-sex hormone (CSH) treatments as part of their treatment plans, with little known about their incidence of breast cancer. This information gap can lead to disparities in the provision of transgender health care. The purpose of the study was to examine th...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-014-3213-2
更新日期:2015-01-01 00:00:00
abstract:PURPOSE:Differences in tumor biology, genomic architecture, and health care delivery patterns contribute to the breast cancer mortality gap between White and Black patients in the US. Although this gap has been well documented in previous literature, it remains uncertain how large the actual effect size of race is for ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-020-05984-w
更新日期:2020-10-27 00:00:00
abstract::Several independent studies have presented evidence for the involvement of human papillomaviruses (HPV) in the aetiology of human breast cancer, while others have reported the opposite findings. Here, we have analysed by a high sensitive multiplex PCR-based method the prevalence of alpha mucosal and beta cutaneous HPV...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-008-0040-3
更新日期:2009-04-01 00:00:00
abstract::The maintenance of hematopoietic progenitor cells as assayed in the mixed colony (CFU-GEMM) assay in human long-term bone marrow cultures was compared between normal allogeneic marrow transplantation donor collections and those from candidates for high-dose therapy and autologous bone marrow transplantation (ABMT). To...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1005732531318
更新日期:1997-06-01 00:00:00
abstract::The clinical benefit of eribulin versus capecitabine was evaluated using health-related quality of life (HRQoL) data from a phase 3 randomized trial in patients with pretreated advanced/metastatic breast cancer (ClinicalTrials.gov identifier: NCT00337103). The study population has been described previously (Kaufman et...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,多中心研究,随机对照试验
doi:10.1007/s10549-015-3633-7
更新日期:2015-12-01 00:00:00
abstract::We examined the role of Mcl-1 and Bcl-2 expression in the induction of apoptosis. through blocking protein tyrosine kinase (PTK), protein kinase C (PKC), phosphatidylinositol 3-kinase (P13-K) and mitogen-activated protein kinase (MAPK)/Erk kinase (MEK) signaling pathways by various kinase inhibitors in MCF-7 breast ca...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1023/a:1012564620853
更新日期:2001-11-01 00:00:00
abstract::The diagnosis and treatment of patients with breast cancer is beginning to be influenced by new ideas and discoveries emerging from the field of angiogenesis research. This field, pursued in the laboratory for more than 20 years, has in the past 5 years generated clinical applications. Some of these applications have ...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/BF00666033
更新日期:1995-01-01 00:00:00
abstract::Epidemiological studies on the association between SULT1A1 codon 213 polymorphism and breast cancer risk are inconclusive. In order to derive a more precise estimation of the association, a meta-analysis was conducted in this article. Sixteen studies including 9,881 cases and 13,564 controls were collected for SULT1A1...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,meta分析
doi:10.1007/s10549-010-0953-5
更新日期:2011-01-01 00:00:00
abstract:PURPOSE:To assess the association between benign ovarian tumors and subsequent risk of breast cancer, and to examine this association according to type of benign ovarian tumors. METHODS:This nationwide cohort study comprised all Danish women diagnosed with a benign ovarian tumor during 1978-2016 (n = 158,221) identifi...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-019-05369-8
更新日期:2019-11-01 00:00:00
abstract::After more than 100 reported randomized trials of systemic adjuvant therapy in breast cancer, it is clear that this therapy will prolong the time to recurrence and the survival time significantly, at least in some patient subsets. But there is less than complete agreement as to which subsets, which therapies, how much...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,随机对照试验,评审
doi:10.1007/BF01805971
更新日期:1989-10-01 00:00:00
abstract:PURPOSE:This project was undertaken to examine the association between dietary intake of soy or cruciferous vegetables and breast cancer treatment-related symptoms among Chinese-American (CA) and Non-Hispanic White (NHW) breast cancer survivors. METHODS:This cross-sectional study included 192 CA and 173 NHW female bre...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-017-4578-9
更新日期:2018-04-01 00:00:00
abstract::We have measured the levels of tamoxifen and three of its metabolites in the blood of patients receiving tamoxifen alone or combination therapy with tamoxifen and medroxyprogesterone acetate. Our results indicate that addition of the progestogen significantly alters the metabolism of tamoxifen over a six-month period....
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF01833345
更新日期:1992-01-01 00:00:00
abstract::There remains a high unmet need for effective treatments for metastatic breast cancer. In recent years there have been many advances in the understanding of biological basis of cancer. Several cellular pathways have been identified that play crucial roles in causing or maintaining the cancer phenotype. Many new agents...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章,评审
doi:10.1007/s10549-008-0268-y
更新日期:2009-07-01 00:00:00
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journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-016-3787-y
更新日期:2016-05-01 00:00:00
abstract::Seroma formation after axillary lymphadenectomy in women with breast cancer remains a problem despite many efforts to reduce surgery-related morbidity. In a prospective, randomised, open, parallel-group, controlled clinical trial we evaluated the effect of a fibrin-glue coated collagen patch (TachoComb H, Nycomed Phar...
journal_title:Breast cancer research and treatment
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1023/a:1010671209279
更新日期:2001-05-01 00:00:00
abstract::Breast cancer is the most common cancer among women. It is estimated that 7% of women who have breast cancer will develop a subsequent second independent breast tumor within 10 years of the first. The status of estrogen (ER), progesterone (PR) and human growth hormone (HER2) receptors, individually and as phenotypic c...
journal_title:Breast cancer research and treatment
pub_type: 杂志文章
doi:10.1007/s10549-009-0469-z
更新日期:2010-02-01 00:00:00