当前位置： SCI文献检索 > MOLECULAR PHARMACOLOGY期刊下所有文献 > BRCA1 contributes to cell cycle arrest and chemoresistance in response to the anticancer agent irofulven.

BRCA1 contributes to cell cycle arrest and chemoresistance in response to the anticancer agent irofulven.

Abstract：

:Tumor suppressor gene BRCA1 is frequently mutated in familial breast and ovarian cancer. BRCA1 plays pivotal roles in maintaining genomic stability by interacting with numerous proteins in cell cycle control and DNA repair. Irofulven (6-hydroxymethylacylfulvene, HMAF, MGI 114, NSC 683863) is one of a new class of anticancer agents that are analogs of mushroom-derived illudin toxins. Preclinical studies and clinical trials have demonstrated that irofulven is effective against several tumor cell types. The exact nature of irofulven-induced DNA damage is not completely understood. We demonstrated previously that irofulven activates ATM and its targets, NBS1, SMC1, CHK2, and p53. In this study, we hypothesize that irofulven induces DNA double-strand breaks and that BRCA1 may affect chemosensitivity by controlling cell cycle checkpoints, DNA repair, and genomic stability in response to irofulven treatment. We observed that irofulven induces the formation of chromosome breaks and radials and the activation and foci formation of gamma-H2AX, BRCA1, and RAD51. We also provided evidence that irofulven induces the generation of DNA double-strand breaks. By using BRCA1-deficient or -proficient cells, we demonstrated that in response to irofulven, BRCA1 contributes to the control of S and G(2)/M cell cycle arrest and is critical for repairing DNA double-strand breaks and for RAD51-dependent homologous recombination. Furthermore, we found that BRCA1 deficiency results in increased chromosome damage and chemosensitivity after irofulven treatment.

journal_name

Mol Pharmacol

journal_title

Molecular pharmacology

authors

Wiltshire T,Senft J,Wang Y,Konat GW,Wenger SL,Reed E,Wang W

doi

10.1124/mol.106.029504

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

1051-60

issue

4

eissn

0026-895X

issn

1521-0111

pii

mol.106.029504

journal_volume

71

pub_type

杂志文章

相关文献

MOLECULAR PHARMACOLOGY文献大全
  • Transforming growth factor-beta 1 down-regulates basal and polycyclic aromatic hydrocarbon-induced cytochromes P-450 1A1 and 1A2 in adult human hepatocytes in primary culture.

    abstract：:The effects of interleukin (IL)-1 beta, IL-4, IL-6, tumor necrosis factor (TNF)-alpha, interferon (IFN)-alpha, IFN-gamma, and transforming growth factor (TGF)-beta 1 on cytochrome P-450 (CYP) 1A expression and polycyclic aromatic hydrocarbon (PAH)-mediated induction in primary human hepatocyte cultures were determined...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Abdel-Razzak Z,Corcos L,Fautrel A,Campion JP,Guillouzo A

    更新日期：1994-12-01 00:00:00

  • 5'-O-tritylated nucleoside derivatives: inhibition of thymidine phosphorylase and angiogenesis.

    abstract：:Thymidine phosphorylase (TPase) is one of the key enzymes involved in the pyrimidine nucleoside salvage pathway. However, TPase also stimulates angiogenesis, and its expression correlates well with microvessel density and metastasis in a variety of human tumors. We have shown recently that 5'-O-trityl-inosine (KIN59) ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.105.021188

    authors： Liekens S,Bronckaers A,Hernández AI,Priego EM,Casanova E,Camarasa MJ,Pérez-Pérez MJ,Balzarini J

    更新日期：2006-08-01 00:00:00

  • Differential activation of human gastrin-releasing peptide receptor-mediated responses by bombesin analogs.

    abstract：:To enable the detailed pharmacological characterization of five bombesin (BN) analogs with respect to the human gastrin-releasing peptide (GRP) receptor, we ectopically expressed the receptor in BALB/3T3 cells. In such cells (termed GR1 cells), GRP stimulated DNA synthesis and Ca2+ mobilization. Two of these analogs, ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Wu JM,Hoang DO,Feldman RI

    更新日期：1995-04-01 00:00:00

  • Chronic selegiline administration transiently decreases tyrosine hydroxylase activity and mRNA in the rat nigrostriatal pathway.

    abstract：:Selegiline, a selective monoamine oxidase type B inhibitor, is beneficial in the treatment of Parkinson's disease. However, this beneficial effect is only transient, and patients must ultimately resort to treatment with standard levodopa therapy. We studied the effects of chronic selegiline treatment on the rat nigros...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Vrana SL,Azzaro AJ,Vrana KE

    更新日期：1992-05-01 00:00:00

  • Photoaffinity cross-linking of a radioiodinated probe, 125I-A55453, into alpha 1-adrenergic receptors.

    abstract：:We have synthesized and characterized a high-affinity alpha 1-adrenergic receptor probe, 4-amino-6,7-dimethoxy-2[4'- [5"(3"'-125I-iodo-4"'-aminophenyl)pentanoyl]-1'-piperazinyl] quinazoline (125I-A55453). This ligand binds reversibly to rat hepatic plasma membranes with high affinity (KD = 77 +/- 6 pM), and it labels ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Dickinson KE,Leeb-Lundberg LM,Heald SL,Wikberg JE,DeBernardis JF,Caron MG,Lefkowitz RJ

    更新日期：1984-09-01 00:00:00

  • Positive cooperativity in the binding of alcuronium and N-methylscopolamine to muscarinic acetylcholine receptors.

    abstract：:The effect of the neuromuscular blocker alcuronium on the binding of N-[3H]-methylscopolamine [( 3H]NMS) and l-[3H]quinuclidinylbenzilate ([3H]QNB) to muscarinic binding sites in rat heart atria, longitudinal smooth muscle of the ileum, cerebral cortex, cerebellum, and submaxillary glands was measured using filtration...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Tucek S,Musílková J,Nedoma J,Proska J,Shelkovnikov S,Vorlícek J

    更新日期：1990-11-01 00:00:00

  • Bryostatin 1 protects protein kinase C-delta from down-regulation in mouse keratinocytes in parallel with its inhibition of phorbol ester-induced differentiation.

    abstract：:Bryostatin 1 and phorbol-12-myristate-13-acetate (PMA) are both potent activators of protein kinase C (PKC), although in primary mouse keratinocytes bryostatin 1 does not induce differentiation and blocks PMA-induced differentiation. We report here that in primary mouse keratinocytes PMA caused translocation of PKC-ep...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Szallasi Z,Denning MF,Smith CB,Dlugosz AA,Yuspa SH,Pettit GR,Blumberg PM

    更新日期：1994-11-01 00:00:00

  • Studies on neuropeptide Y receptors in a mouse adrenocortical cell line.

    abstract：:The mouse adrenocortical Y-1 cell line has been found to express high affinity binding sites for neuropeptide Y (NPY). Pharmacological studies have shown that these NPY binding sites are of the Y1 type. Reverse transcription-polymerase chain reaction using primers specific for the rat Y1 receptor revealed that the NPY...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Weng G,Yee F,Michl P,Reis D,Wahlestedt C

    更新日期：1995-07-01 00:00:00

  • AKT1, LKB1, and YAP1 Revealed as MYC Interactors with NanoLuc-Based Protein-Fragment Complementation Assay.

    abstract：:The c-Myc (MYC) transcription factor is a major cancer driver and a well-validated therapeutic target. However, directly targeting MYC has been challenging. Thus, identifying proteins that interact with and regulate MYC may provide alternative strategies to inhibit its oncogenic activity. In this study, we report the ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.116.107623

    authors： Mo X,Qi Q,Ivanov AA,Niu Q,Luo Y,Havel J,Goetze R,Bell S,Moreno CS,Cooper LA,Johns MA,Khuri FR,Du Y,Fu H

    更新日期：2017-04-01 00:00:00

  • Species-specific differences in translational regulation of dihydrofolate reductase.

    abstract：:We have observed that rodent cell lines (mouse, hamster) contain approximately 10 times the levels of dihydrofolate reductase as human cell lines, yet the sensitivity to methotrexate (ED(50)), the folate antagonist that targets this enzyme, is similar. Our previous studies showed that dihydrofolate reductase protein l...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.109.055772

    authors： Hsieh YC,Skacel NE,Bansal N,Scotto KW,Banerjee D,Bertino JR,Abali EE

    更新日期：2009-10-01 00:00:00

  • A novel metabotropic glutamate receptor 5 positive allosteric modulator acts at a unique site and confers stimulus bias to mGlu5 signaling.

    abstract：:Metabotropic glutamate receptor 5 (mGlu5) is a target for the treatment of central nervous system (CNS) disorders, such as schizophrenia and Alzheimer's disease. Furthermore, mGlu5 has been shown to play an important role in hippocampal synaptic plasticity, specifically in long-term depression (LTD) and long-term pote...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.112.082891

    authors： Noetzel MJ,Gregory KJ,Vinson PN,Manka JT,Stauffer SR,Lindsley CW,Niswender CM,Xiang Z,Conn PJ

    更新日期：2013-04-01 00:00:00

  • Characterization of thrombin-bound dabigatran effects on protease-activated receptor-1 expression and signaling in vitro.

    abstract：:Thrombin, the key effector protease of the coagulation cascade, drives fibrin deposition and activates human platelets through protease-activated receptor-1 (PAR1). These processes are critical to the progression of thrombotic diseases. Thrombin is the main target of anticoagulant therapy, and major efforts have led t...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.114.096446

    authors： Chen B,Soto AG,Coronel LJ,Goss A,van Ryn J,Trejo J

    更新日期：2015-07-01 00:00:00

  • Identification of three separate guanine nucleotide-binding proteins that interact with the delta-opioid receptor in NG108-15 neuroblastoma x glioma hybrid cells.

    abstract：:Five separate guanine nucleotide-binding proteins (G proteins) were immunologically identified in membranes from neuroblastoma x glioma NG108-15 hybrid cells. These alpha subunit proteins were Gi2 alpha, two isoforms of Gi3 alpha, and two isoforms of Go alpha. The G proteins that interacted with delta-opioid receptors...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Roerig SC,Loh HH,Law PY

    更新日期：1992-05-01 00:00:00

  • PAR1 and PAR2 couple to overlapping and distinct sets of G proteins and linked signaling pathways to differentially regulate cell physiology.

    abstract：:The protease-activated receptors (PAR1 and PAR2) are unusual G protein-coupled receptors that are activated by distinct serine proteases and are coexpressed in many different cell types. Limited recent evidence suggests these closely related receptors regulate different physiological outputs in the same cell, although...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.109.062018

    authors： McCoy KL,Traynelis SF,Hepler JR

    更新日期：2010-06-01 00:00:00

  • Identification of a human gastrointestinal tract and immune system receptor for the peptide neuromedin U.

    abstract：:Neuromedin U (NmU) is a 25 amino acid peptide prominently expressed in the upper gastrointestinal (GI) tract and central nervous system. It is highly conserved throughout evolution and induces smooth muscle contraction in a variety of species. Our understanding of NmU biology has been limited because the identity of i...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.58.4.870

    authors： Hedrick JA,Morse K,Shan L,Qiao X,Pang L,Wang S,Laz T,Gustafson EL,Bayne M,Monsma FJ Jr

    更新日期：2000-10-01 00:00:00

  • Hemodynamic Effects of Glutathione-Liganded Binuclear Dinitrosyl Iron Complex: Evidence for Nitroxyl Generation and Modulation by Plasma Albumin.

    abstract：:Glutathione-liganded binuclear dinitrosyl iron complex (glut-BDNIC) has been proposed to be a donor of nitric oxide (NO). This study was undertaken to investigate the mechanisms of vasoactivity, systemic hemodynamic effects, and pharmacokinetics of glut-BDNIC. To test the hypothesis that glut-BDNICs vasodilate by rele...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.117.110957

    authors： Liu T,Zhang M,Terry MH,Schroeder H,Wilson SM,Power GG,Li Q,Tipple TE,Borchardt D,Blood AB

    更新日期：2018-05-01 00:00:00

  • Protein RS1 (RSC1A1) Downregulates the Exocytotic Pathway of Glucose Transporter SGLT1 at Low Intracellular Glucose via Inhibition of Ornithine Decarboxylase.

    abstract：:Na+-d-glucose cotransporter 1 (SGLT1) is rate-limiting for glucose absorption in the small intestine. Shortly after intake of glucose-rich food, SGLT1 abundance in the luminal membrane of the small intestine is increased. This upregulation occurs via glucose-induced acceleration of the release of SGLT1-containing vesi...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.116.104521

    authors： Chintalapati C,Keller T,Mueller TD,Gorboulev V,Schäfer N,Zilkowski I,Veyhl-Wichmann M,Geiger D,Groll J,Koepsell H

    更新日期：2016-11-01 00:00:00

  • RNA interference-mediated knockdown of dynamin 2 reduces endocannabinoid uptake into neuronal dCAD cells.

    abstract：:The precise mechanism by which the cellular uptake of the endocannabinoid anandamide (AEA) occurs has been the source of much debate. In the current study, we show that neuronal differentiated CAD (dCAD) cells accumulate anandamide by a process that is inhibited in a dose-dependent manner by N-(4-hydroxyphenyl)arachid...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.108.044834

    authors： McFarland MJ,Bardell TK,Yates ML,Placzek EA,Barker EL

    更新日期：2008-07-01 00:00:00

  • Disposition of homocysteine and S-3-deazaadenosylhomocysteine in cells exposed to 3-deazaadenosine.

    abstract：:The nucleoside analogue, 3-deazaadenosine (c3-Ado), serves both as a substrate and as an inhibitor of S-adenosylhomocysteine (AdoHcy) hydrolase, and the ability of this compound to induce accumulation of intracellular AdoHcy and S-3-deazaadenosylhomocysteine (c3-AdoHcy) in various cells and species has been widely doc...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Svardal A,Djurhuus R,Ueland PM

    更新日期：1986-08-01 00:00:00

  • A naturally occurring tyrosine to histidine replacement at residue 33 of human thymidylate synthase confers resistance to 5-fluoro-2'-deoxyuridine in mammalian and bacterial cells.

    abstract：:Structural changes in the macromolecular targets of pharmacological agents can result in alterations in the efficacy of these agents. In previous studies, we identified a variant structural form of thymidylate synthase (TS) that is associated with relative resistance to 5-fluoro-2'-deoxyuridine, in a human colonic tum...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Barbour KW,Hoganson DK,Berger SH,Berger FG

    更新日期：1992-08-01 00:00:00

  • Activation of the mitogen activated protein kinase extracellular signal-regulated kinase 1 and 2 by the nitric oxide-cGMP-cGMP-dependent protein kinase axis regulates the expression of matrix metalloproteinase 13 in vascular endothelial cells.

    abstract：:Matrix metalloproteinases (MMPs) are synthesized in response to diverse stimuli, including cytokines, growth factors, hormones, and oxidative stress. Here we show that the nitric oxide (NO) donor 2-(N,N-diethylamino)-diazenolate-2-oxide (DEA-NO) and NO from murine macrophages transcriptionally regulate MMP-13 expressi...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.62.4.927

    authors： Zaragoza C,Soria E,López E,Browning D,Balbín M,López-Otín C,Lamas S

    更新日期：2002-10-01 00:00:00

  • Examination of the mechanism(s) involved in doxorubicin-mediated iron accumulation in ferritin: studies using metabolic inhibitors, protein synthesis inhibitors, and lysosomotropic agents.

    abstract：:Anthracyclines are potent anticancer agents, but their use is limited by cardiotoxicity at high cumulative doses. The mechanisms involved in anthracycline-mediated cardiotoxicity are still poorly understood, but numerous investigations have indicated a role for iron in this process. Our previous studies using neoplast...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.65.1.181

    authors： Kwok JC,Richardson DR

    更新日期：2004-01-01 00:00:00

  • Modulators of CXCR4 and CXCR7/ACKR3 Function.

    abstract：:The two G protein-coupled receptors (GPCRs) C-X-C chemokine receptor type 4 (CXCR4) and atypical chemokine receptor 3 (ACKR3) are part of the class A chemokine GPCR family and represent important drug targets for human immunodeficiency virus (HIV) infection, cancer, and inflammation diseases. CXCR4 is one of only thre...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章,评审

    doi：10.1124/mol.119.117663

    authors： Adlere I,Caspar B,Arimont M,Dekkers S,Visser K,Stuijt J,de Graaf C,Stocks M,Kellam B,Briddon S,Wijtmans M,de Esch I,Hill S,Leurs R

    更新日期：2019-12-01 00:00:00

  • Mutations at lipid-exposed residues of the acetylcholine receptor affect its gating kinetics.

    abstract：:The firmest candidate among the transmembrane portions of the nicotinic acetylcholine receptor (AChR) to be in contact with the lipid bilayer is the fourth segment, M4. To explore the contribution of alphaM4 amino acid residues of mouse AChR to channel gating, we combined site-directed mutagenesis with single-channel ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.54.1.146

    authors： Bouzat C,Roccamo AM,Garbus I,Barrantes FJ

    更新日期：1998-07-01 00:00:00

  • Structural Basis for Diltiazem Block of a Voltage-Gated Ca2+ Channel.

    abstract：:Diltiazem is a widely prescribed Ca2+ antagonist drug for cardiac arrhythmia, hypertension, and angina pectoris. Using the ancestral CaV channel construct CaVAb as a molecular model for X-ray crystallographic analysis, we show here that diltiazem targets the central cavity of the voltage-gated Ca2+ channel underneath ...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.119.117531

    authors： Tang L,Gamal El-Din TM,Lenaeus MJ,Zheng N,Catterall WA

    更新日期：2019-10-01 00:00:00

  • Neuritogenic Activity of Tetradecyl 2,3-Dihydroxybenzoate Is Mediated through the Insulin-Like Growth Factor 1 Receptor/Phosphatidylinositol 3 Kinase/Mitogen-Activated Protein Kinase Signaling Pathway.

    abstract：:Tetradecyl 2,3-dihydroxybenzoate (ABG-001) is a lead compound derived from neuritogenic gentisides. In the present study, we investigated the mechanism by which ABG-001 induces neurite outgrowth in a rat adrenal pheochromocytoma cell line (PC12). Inhibitors of insulin-like growth factor 1 (IGF-1) receptor, phosphatidy...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.115.097758

    authors： Tang R,Gao L,Kawatani M,Chen J,Cao X,Osada H,Xiang L,Qi J

    更新日期：2015-08-01 00:00:00

  • Lipoxygenase metabolites as mediators of UTP-induced intracellular acidification in mouse RAW 264.7 macrophages.

    abstract：:In previous studies, we have shown that mouse RAW 264.7 macrophages possess pyrimidinoceptors, coupled to a phosphoinositide-specific phospholipase C, with a higher specificity for UTP than for ATP. In the current study, we explored the mechanism involved in the UTP-induced intracellular acidification seen in this cel...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.53.2.313

    authors： Lin WW,Chang SH,Wu ML

    更新日期：1998-02-01 00:00:00

  • Thyrotropin activates mitogen-activated protein kinase pathway in FRTL-5 by a cAMP-dependent protein kinase A-independent mechanism.

    abstract：:The involvement of mitogen-activated protein (MAP) kinases in the mitogenic effect of thyrotropin (TSH) is not fully elucidated. In FRTL-5 cells, we found that the MAP kinase kinase (MEK) inhibitors UO126 and PD98059 substantially decreased TSH-induced DNA synthesis, indicating that MAP kinases are involved in the TSH...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：10.1124/mol.60.5.924

    authors： Iacovelli L,Capobianco L,Salvatore L,Sallese M,D'Ancona GM,De Blasi A

    更新日期：2001-11-01 00:00:00

  • Importance of valine at position 152 for the substrate transport and 2beta-carbomethoxy-3beta-(4-fluorophenyl)tropane binding of dopamine transporter.

    abstract：:Human and bovine dopamine transporters (DAT) demonstrate discrete functional differences in dopamine (DA), 1-methyl-4-phenylpyridium (MPP(+)) transport, and cocaine analog binding. In a previous study, the functional analyses on the chimeras of human and bovine DAT have revealed that the region from residues 133 throu...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Lee SH,Chang MY,Lee KH,Park BS,Lee YS,Chin HR,Lee YS

    更新日期：2000-05-01 00:00:00

  • Comparison of two putatively selective radioligands for labeling central nervous system beta-adrenergic receptors: inadequacy of [3H]dihydroalprenolol.

    abstract：:[3H]Dihydroalprenolol ([3H]DHA) has been used extensively in receptor binding studies to measure beta-adrenergic receptors in the central nervous system. Usually, nonspecific binding has been defined by high concentrations of the beta-adrenergic receptor agonist isoproterenol or antagonists such as alprenolol or propr...

    journal_title：Molecular pharmacology

    pub_type： 杂志文章

    doi：

    authors： Riva MA,Creese I

    更新日期：1989-07-01 00:00:00