Abstract:
:The tumor suppressor protein BRCA1 localizes to sites of DNA double-strand breaks (DSB), promoting repair by homologous recombination through the recruitment of DNA damage repair proteins. In normal cells, homologous recombination largely depends on BRCA1. However, assembly of the pivotal homologous recombination regulator RAD51 can occur independently of BRCA1 in the absence of 53BP1, another DNA damage response protein. How this assembly process proceeds is unclear, but important to understand in tumor cell settings where BRCA1 is disabled. Here we report that RNF8 regulates BRCA1-independent homologous recombination in 53BP1-depleted cells. RNF8 depletion suppressed the recruitment of RAD51 to DSB sites without affecting assembly or phosphorylation of the replication protein RPA in neocarzinostatin-treated or X-ray-irradiated BRCA1/53BP1-depleted cells. Furthermore, RNF8/BRCA1/53BP1-depleted cells exhibited less efficient homologous recombination than BRCA1/53BP1-depleted cells. Intriguingly, neither RNF8 nor its relative RNF168 were required for RAD51 assembly at DSB sites in 53BP1-expressing cells. Moreover, RNF8-independent RAD51 assembly was found to be regulated by BRCA1. Together, our findings indicate a tripartite regulation of homologous recombination by RNF8, BRCA1, and 53BP1. In addition, our results predict that RNF8 inhibition may be a useful treatment of BRCA1-mutated/53BP1(low) cancers, which are considered resistant to treatment by PARP1 inhibitors and of marked current clinical interest.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Nakada S,Yonamine RM,Matsuo Kdoi
10.1158/0008-5472.CAN-12-1057subject
Has Abstractpub_date
2012-10-01 00:00:00pages
4974-83issue
19eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-12-1057journal_volume
72pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::In this matched case-control study nested within the prospective Physicians' Health Study, we evaluated whether DNA damage in blood samples collected at enrollment significantly predicted risk, consistent with our hypothesis that cases have greater biological susceptibility to polycyclic aromatic hydrocarbons and othe...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-09-15 00:00:00
abstract::The interaction between platelets and tumor cells is important in the formation of pulmonary metastasis. We previously established the 8F11 monoclonal antibody (mAb) by immunizing rats with the NL-17 cell line, a highly metastatic variant of mouse colon adenocarcinoma 26. 8F11 could inhibit the platelet aggregation in...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-07-15 00:00:00
abstract::The aim of the present study was to establish screening biomarkers of exposure to antineoplastic drugs administered to 11 patients undergoing cancer chemotherapy. Among the anticancer drugs administered were cyclophosphamide (all), Adriamycin (5 of 11), methotrexate (3 of 11), 5-fluorouracil (4 of 11), vincristine (3 ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-06-01 00:00:00
abstract::CAMA-1 cells, isolated from malignant pleural effusion, are grown in long-term cultures as monolayers. The rate of growth is dependent upon fetal bovine serum and estradiol. These cells also exhibit a dose response to added 17 beta-estradiol with respect to the incorporation of radiolabeled thymidine into cells. The u...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-12-01 00:00:00
abstract::A simple technique is described for fixing colony-containing layers of soft agar and drying them onto microscopic slides. The method is extrapolated from techniques used in immunology for permanent preservation of immunodiffusion or immunoelectrophoresis plates. Slides prepared in this fashion are eminently suitable f...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-03-01 00:00:00
abstract::Cyclophosphamide treatment of adult male rats leads to sustained decreases in several liver microsomal cytochrome P450 (CYP) activities, including CYP 2C11-catalyzed cyclophosphamide activation, via a process that is associated with a feminization of the overall pattern of liver enzyme expression (G. A. LeBlanc and D....
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-06-01 00:00:00
abstract::Mutations in the p53 tumor suppressor gene have been demonstrated to be one of the most frequent genetic abnormalities in human cancers. Previous studies have shown that the frequency of p53 mutations is significantly higher in small cell lung cancer than in non-small cell lung cancer. However, this conclusion was bas...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-11-15 00:00:00
abstract::One limitation of autologous bone marrow transplantation for patients with cancer has been the presence of tumor cells in the bone marrow. Methods to eliminate tumor cells while preserving hematopoietic stem cells have been sought. The present study was performed to analyze the in vitro effectiveness of light-activate...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-07-01 00:00:00
abstract::DNA synthesis was studied in mouse ascites sarcoma cells using a permeable cell system. The sarcoma was induced by the Schmidt-Ruppin strain of Rous sarcoma virus. The cells were made permeable to nucleoside triphosphates by treatment with a hypotonic buffer containing 10 mM Tris Cl, 4 mM MgCl2, 1 mM EDTA, and 6 mM 2-...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-01-01 00:00:00
abstract::A method was elaborated for high-yield 125I-trap labeling of rat colon carcinoma cells using conjugates of dichlorotriazine aminofluorescein and bovine serum albumin substituted with either N-acetylgalactosamine or N-acetylglucosamine as vehicles. Fluorescence microscopy revealed that the ligands accumulated in perinu...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-02-01 00:00:00
abstract::Breast carcinomas < or = 1 cm in size (T1a,b) are being detected more frequently as a result of screening. Because traditional prognostic parameters are either lacking (tumor size) or rare (nodal metastases), a marker(s) is needed to identify the subset of patients who could benefit from adjuvant therapy. A retrospect...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-04-01 00:00:00
abstract::SMYD3 methyltransferase is nearly undetectable in normal human tissues but highly expressed in several cancers, including breast cancer, although its contributions to pathogenesis in this setting are unclear. Here we report that histone H2A.Z.1 is a substrate of SMYD3 that supports malignancy. SMYD3-mediated dimethyla...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-0500
更新日期:2016-10-15 00:00:00
abstract::A mouse IgG2a monoclonal antibody, SWA20, defining a tumor-associated cell surface antigen on small cell carcinoma of the lung (SCC) was generated. The reactivity of the antibody with cell lines was examined by indirect immunofluorescence staining and solid phase radioimmunoassay and the reactivity with tissues by imm...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-08-01 00:00:00
abstract::Human tumor cells containing ras oncogenes display enhanced sensitivity to 1-beta-D-arabinofuranosylcytosine (Ara-C) and other deoxycytidine analogues (H-M. Koo, et al., Cancer Res., 56: 5211-5216, 1996). Human tumor cell lines with or without a ras oncogene as well as a pair of isogenic cell lines with one containing...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-12-15 00:00:00
abstract::Phosphatidylinositol-3-kinase is an important enzyme for intracellular signaling. The microbial product wortmannin and some of its analogues have been shown to be potent inhibitors of phosphatidylinositol-3-kinase. The 50% inhibitory concentration for inhibition by wortmannin is 2 to 4 nM. Kinetic analysis demonstrate...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-05-01 00:00:00
abstract::In previous studies, we reported that key antioxidant and DNA repair genes are regulated differently in normal bronchial epithelial cells of lung cancer cases compared with non-lung cancer controls. In an effort to develop a biomarker for lung cancer risk, we evaluated the transcript expressions of 14 antioxidant, DNA...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-1568
更新日期:2009-11-15 00:00:00
abstract::Angiostatin, a proteolytic fragment of plasminogen, is a potent angiogenesis inhibitor able to suppress tumor growth and metastasis through inhibition of endothelial cell proliferation and migration. Previously, we showed that angiostatin binds and inhibits F(1)F(o) ATP synthase on the endothelial cell surface and tha...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-2806
更新日期:2006-01-15 00:00:00
abstract::We examined the DNA methylation pathway in an autochthonous murine prostate cancer model, transgenic adenocarcinoma of mouse prostate (TRAMP). We observed that, compared with strain-matched normal prostates, primary and metastatic TRAMP tumors display increased cytosine DNA methyltransferase (Dnmt) activity, Dnmt1 and...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-1937
更新日期:2006-12-15 00:00:00
abstract::Murine monoclonal antibodies of the immunoglobulin G2a isotype interact with human effector cells to mediate antibody-dependent cellular cytotoxicity (ADCC) directed against malignant cells which express antigens recognized by these antibodies. gamma-Interferon enhances these effects in vitro. In a Phase I trial of mu...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-05-01 00:00:00
abstract::Chromosomal passenger complex (CPC) has been demonstrated to be a potential target of cancer therapy by inhibiting Aurora B or survivin in different types of cancer including neuroblastoma. However, chemical inhibition of either Aurora B or survivin does not target CPC specifically due to off-target effects or CPC-ind...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-19-0695
更新日期:2019-10-01 00:00:00
abstract::We have synthesized fluoromycin (FLM), a novel fluorescein-labeled derivative of talisomycin S10b (TLM S10b), and used it to evaluate cellular drug accumulation and distribution in bleomycin (BLM)-sensitive and -resistant cell lines. The fluorescence intensity of FLM was 300- to 400-fold greater than that of BLM A2, T...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-02-01 00:00:00
abstract::The monoclonal antibodies (MAbs) 323/A3 and 17-1A both recognize a 40-kDa carcinoma-associated epithelial glycoprotein (EGP40). MAb 17-1A has been used in many therapeutic trials as an immunotherapeutic agent to combat advanced colorectal cancer, and about 5-10% overall responses have been observed. It has been shown ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-04-01 00:00:00
abstract::The epithelial-to-mesenchymal transition (EMT) is a reversible process comprised of various subprograms via which epithelial cells reduce their intercellular adhesions and proliferative capacity while gaining a mesenchymal phenotype with increased migratory and invasive properties. This process has been well described...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-17-0032
更新日期:2017-09-01 00:00:00
abstract::The efficacy of novel cancer therapeutics has been hampered by the ability to deliver these agents to the tumor at effective concentrations. Liposomes have been used as a method to overcome some delivery issues and, in combination with hyperthermia, have been shown to increase drug delivery to tumors. Particle size ha...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-08-15 00:00:00
abstract::Hypoxia-inducible factor (HIF)-1, a heterodimeric transcription factor composed of HIF-1alpha and HIF-1beta subunits coordinates pathophysiologic responses toward decreased oxygen availability. It is now appreciated that enhanced protein translation of HIF-1alpha under normoxia accounts for an alternative regulatory c...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-1437
更新日期:2004-12-15 00:00:00
abstract::Cancer immunotherapy may become a major treatment backbone in many cancers over the next decade. There are numerous immune cell types found in cancers and many components of an immune reaction to cancer. Thus, the tumor has many strategies to evade an immune response. It has been proposed that four different types of ...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-15-0255
更新日期:2015-06-01 00:00:00
abstract::The human MAGE-3 gene encodes a melanoma antigenic epitope recognized by specific cytotoxic T lymphocytes, but its gene product has not been identified thus far. We produced a recombinant MAGE-3 gene product by expression cloning of the entire reading frame in the context of a fusion protein characterized by a 10-hist...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-06-01 00:00:00
abstract::In the era of omics-driven research, it remains a common dilemma to stratify individual patients based on the molecular characteristics of their tumors. To improve molecular stratification of patients with breast cancer, we developed the Gaussian mixture model (GMM)-based classifier. This probabilistic classifier was ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-19-0573
更新日期:2019-07-01 00:00:00
abstract::Picroliv, an iridoid glycoside derived from the plant Picrorhiza kurroa, is used traditionally to treat fever, asthma, hepatitis, and other inflammatory conditions. However, the exact mechanism of its therapeutic action is still unknown. Because nuclear factor-kappaB (NF-kappaB) activation plays a major role in inflam...
journal_title:Cancer research
pub_type: 杂志文章,收录出版
doi:10.1158/0008-5472.CAN-08-1902
更新日期:2008-11-01 00:00:00
abstract::Disease recurrence and metastasis are frequently observed in many successfullytreated localized cancers, including hepatocellular carcinoma in which intrahepatic and extrahepatic recurrence (metastasis) are frequently observed after curative resection. The present study aimed at identifying metastasis-associated genes...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-08-15 00:00:00