Abstract:
:RECQL1, a key member of the RecQ family of DNA helicases, is required for DNA replication and DNA repair. Two recent studies have shown that germline RECQL1 mutations are associated with increased breast cancer susceptibility. Whether altered RECQL1 expression has clinicopathologic significance in sporadic breast cancers is unknown. We evaluated RECQL1 at the transcriptomic level (METABRIC cohort, n = 1,977) and at the protein level [cohort 1, n = 897; cohort 2, n = 252; cohort 3 (BRCA germline deficient), n = 74]. In RECQL1-depleted breast cancer cells, we investigated anthracycline sensitivity. High RECQL1 mRNA was associated with intClust.3 (P = 0.026), which is characterized by low genomic instability. On the other hand, low RECQL1 mRNA was linked to intClust.8 [luminal A estrogen receptor-positive (ER+) subgroup; P = 0.0455] and intClust.9 (luminal B ER+ subgroup; P = 0.0346) molecular phenotypes. Low RECQL1 expression was associated with shorter breast cancer-specific survival (P = 0.001). At the protein level, low nuclear RECQL1 level was associated with larger tumor size, lymph node positivity, high tumor grade, high mitotic index, pleomorphism, dedifferentiation, ER negativity, and HER-2 overexpression (P < 0.05). In ER+ tumors that received endocrine therapy, low RECQL1 was associated with poor survival (P = 0.008). However, in ER- tumors that received anthracycline-based chemotherapy, high RECQL1 was associated with poor survival (P = 0.048). In RECQL1-depleted breast cancer cell lines, we confirmed doxorubicin sensitivity, which was associated with DNA double-strand breaks accumulation, S-phase cell-cycle arrest, and apoptosis. We conclude that RECQL1 has prognostic and predictive significance in breast cancers. Mol Cancer Ther; 16(1); 239-50. ©2016 AACR.
journal_name
Mol Cancer Therjournal_title
Molecular cancer therapeuticsauthors
Arora A,Parvathaneni S,Aleskandarany MA,Agarwal D,Ali R,Abdel-Fatah T,Green AR,Ball GR,Rakha EA,Ellis IO,Sharma S,Madhusudan Sdoi
10.1158/1535-7163.MCT-16-0290subject
Has Abstractpub_date
2017-01-01 00:00:00pages
239-250issue
1eissn
1535-7163issn
1538-8514pii
1535-7163.MCT-16-0290journal_volume
16pub_type
杂志文章abstract::Extensive efforts are under way to identify antiangiogenic therapies for the treatment of human cancers. Many proposed therapeutics target vascular endothelial growth factor (VEGF) or the kinase insert domain receptor (KDR/VEGF receptor-2/FLK-1), the mitogenic VEGF receptor tyrosine kinase expressed by endothelial cel...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-04-0209
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-06-0421
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-14-0280
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-09-0774
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-06-0426
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-18-0558
更新日期:2019-03-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-17-0916
更新日期:2018-10-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-13-0924
更新日期:2014-05-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-19-1064
更新日期:2020-08-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:
更新日期:2004-05-01 00:00:00
abstract::Repurposing cationic amphiphilic drugs (CAD) for cancer treatment is emerging as an attractive means to enhance the efficacy of chemotherapy. Many commonly used CADs, including several cation amphiphilic antihistamines and antidepressants, induce cancer-specific, lysosome-dependent cell death and sensitize cancer cell...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-18-1406
更新日期:2019-09-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-05-0418
更新日期:2006-03-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-12-0644-T
更新日期:2012-11-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-07-0132
更新日期:2007-08-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-09-0543
更新日期:2009-12-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-07-0491
更新日期:2008-01-01 00:00:00
abstract::We previously reported that the EGFR-targeted inhibitor erlotinib induces G1 arrest of squamous cell carcinoma of the head and neck (SCCHN) cell lines without inducing significant apoptosis. Large-scale genomic studies suggest that >50% of SCCHN cases have activation of PI3K pathways. This study investigated whether c...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-16-0683
更新日期:2017-04-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-05-0190
更新日期:2006-02-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:
更新日期:2003-08-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-16-0580
更新日期:2017-06-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-16-0452
更新日期:2017-11-01 00:00:00
abstract::HER3 is overexpressed in several cancers, including colorectal cancer. Although therapies with anti-HER3 antibodies have been investigated, significant clinical benefits have not been reported. U3-1402 is a novel HER3-antibody-drug conjugate (ADC) composed of the HER3 antibody patritumab and a novel topoisomerase I in...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-19-0452
更新日期:2019-11-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-16-0207
更新日期:2016-09-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-17-0634
更新日期:2018-04-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-14-0399
更新日期:2015-01-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:
更新日期:2002-10-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-18-0328
更新日期:2019-01-01 00:00:00
abstract::Hodgkin-Reed/Sternberg (HRS) cells of classical Hodgkin lymphoma show aberrant expression and activation of several receptor tyrosine kinases (RTK) in the majority of cases. Therefore, we tested whether tyrosine kinase inhibitors (TKI) already in clinical use or late stages of clinical trials have antiproliferative ef...
journal_title:Molecular cancer therapeutics
pub_type: 杂志文章
doi:10.1158/1535-7163.MCT-12-0532
更新日期:2013-02-01 00:00:00
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journal_title:Molecular cancer therapeutics
pub_type: 杂志文章,评审
doi:10.1158/1535-7163.MCT-18-0124
更新日期:2018-09-01 00:00:00