Abstract:
:BAG-1 is a multifunctional protein that interacts with a wide range of cellular targets. There is accumulating evidence that overexpression of BAG-1 may play an important role in breast cancer; however, the functional consequences of BAG-1 expression and its mechanism of action in breast cancer cells have not been studied in detail. Here we demonstrate that BAG-1 overexpression completely protected breast cancer cells from apoptosis and long-term growth inhibition induced by heat shock and also partially protected cells from other stresses, including hypoxia, radiation, and chemotoxic drugs. BAG-1 exists as three protein isoforms, and all isoforms prevented stress-induced growth inhibition. This required a conserved lysine in the BAG-1S ubiquitin-like domain thought to be important for proteasome binding and COOH-terminal amino acids required for interaction with the chaperone molecules, Hsc70 and Hsp70. Although expression of BAG-1 was unaltered by heat shock, endogenous and overexpressed BAG-1S relocalized from the cytoplasm to the nucleus after heat shock. The endogenous BAG-1S.Hsc70/Hsp70 complex dissociated after heat shock but was maintained at a detectable level in cells overexpressing BAG-1S. BAG-1-mediated resistance to stress-induced growth inhibition is likely to have a major impact on the development and response to therapy of breast cancer. Targeting the interaction of BAG-1 with chaperones is an attractive strategy to counter the biological effects of BAG-1.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Townsend PA,Cutress RI,Sharp A,Brimmell M,Packham Gsubject
Has Abstractpub_date
2003-07-15 00:00:00pages
4150-7issue
14eissn
0008-5472issn
1538-7445journal_volume
63pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Ewing sarcoma is a rare but aggressive disease most common in young adults. This cancer is driven by a unique chimeric fusion oncogene but targeted strategies have been elusive. Here we report the identification of the protein kinase PKC-ß (PRKCB) as a disease-specific druggable target for treatment of Ewing sarcoma. ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-12-0371
更新日期:2012-09-01 00:00:00
abstract::Medulloblastoma (MB) represents the most frequent malignant brain tumor of childhood but only a few cell lines and animal models of this primitive neuroectodermal tumor (PNET) have thus far been established. Using specific cell culture conditions, we were able to derive four human MB cell lines (MHH-MED-1-4) as well a...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-06-15 00:00:00
abstract::With normal human skin fibroblasts in culture, a transient decrease in queuine modification of tRNA precedes a phorbol ester tumor promoter-induced 5- to 10-fold increase in saturation density. Subsequently, an increase in the queuine content of cellular tRNA (to levels comparable to those in untreated cultures) prece...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1984-08-01 00:00:00
abstract::Axillary lymph node dissection (ALND) has been a part of breast cancer management since the 1900s. The idea that axillary metastases do not require surgical removal is a repudiation of the Halstedian concept of breast cancer biology, yet multiple prospective randomized studies show that the incidence of nodal recurren...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-13-1888
更新日期:2013-12-15 00:00:00
abstract::Since the sodium salt of ascorbic acid (AA) promoted two-stage urinary bladder carcinogenesis in rats, whereas AA itself did not, the roles of the urinary sodium ion concentration and pH on urinary bladder carcinogenesis were investigated. Male F344 rats were given 0.05% N-butyl-N-(4-hydroxybutyl)nitrosamine in their ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-04-01 00:00:00
abstract::Allelic loss of chromosome 9p21 is common in small cell lung cancer (SCLC), but inactivation of the tumor suppressor gene CDKN2a is rare, implying the existence of another target gene at 9p21. A recent deletion mapping study of chromosome 9p has also identified a site of deletion in non-small cell lung cancer (NSCLC) ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-12-01 00:00:00
abstract::One hundred eighty-four cases of feline leukemia and lymphoma diagnosed in Boston from 1972 through 1976 were investigated. Fifty-eight % of these cases were lymphoma, and 42% were leukemia. Sixty-seven % of the cats had positive fluorescent antibody tests for circulating feline leukemia virus. The rest (33%) were vir...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-10-01 00:00:00
abstract::Von Hippel-Lindau (VHL) tumor suppressor protein is expressed in neurons of the central nervous system and plays an important role during the neuronal differentiation of central nervous system progenitor cells. To elucidate the neuronal differentiating potential of VHL protein in neuroblastoma cells, we overexpressed ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-12-01 00:00:00
abstract::Strategies for the prevention of cancer include those aimed at reducing the incidence of cancer (primary prevention) and cancer mortality through early detection of tumors (secondary prevention). The efficacy of prevention interventions is evaluated by clinical trials. The conduct of clinical trials is aided by the us...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:
更新日期:1994-04-01 00:00:00
abstract::Clonal variants of mouse epidermal JB6 cells that are genetically susceptible (P+) or resistant (P-) to tumor promoter-induced neoplastic transformation exhibit differential activator protein-1 (AP-1) response. Transactivation of AP-1 appears to be necessary but not sufficient to promote transformation in JB6 cells. I...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-05-15 00:00:00
abstract::Bone marrow biopsy specimens from patients with myeloma were cultured in either 1 of 2 thin-film culture systems, a controlled environment steady state system or a rocker tube configuration of the system, for periods up to 42 days. Both functional and morphological characteristics of the myeloma cells were well-mainta...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-04-01 00:00:00
abstract::Thioether-lysophospholipids inhibited the in vitro incorporation of [3H]thymidine into blasts of 8 leukemias, lymphocytes of 3 chronic lymphocytic leukemias, and cells of 12 different solid tumors of human origin. This effect correlated with trypan blue dye exclusion, which was used to assess cell damage. Scanning ele...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-11-01 00:00:00
abstract::Human CYP2A6 has been recognized as being involved in the mutagenic activation of promutagens such as the tobacco-specific nitrosamine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK). Methoxsalen (8-methoxypsoralen) was reported to inhibit CYP2A6. In the present study, the inhibitory effects of methoxsalen on NN...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-11-15 00:00:00
abstract::Angiogenesis is characteristic of solid tumor growth and a surrogate marker for metastasis in many human cancers. Inhibition of tumor angiogenesis using antiangiogenic drugs and gene transfer approaches has suggested the potential of this form of therapy in controlling tumor growth. However, for long-term tumor-free s...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.can-03-1786
更新日期:2004-03-01 00:00:00
abstract::The phosphatidylinositol 3' kinase/Akt pathway is frequently dysregulated in cancer, which can have unfavorable consequences in terms of cell proliferation, survival, metabolism, and migration. Increasing evidence suggests that Akt1, Akt2, and Akt3 play unique roles in breast cancer initiation and progression. We have...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-10-0266
更新日期:2010-06-01 00:00:00
abstract::The molecular genetic events involved in the etiology of human granulosa cell (GC) tumors, which represent approximately 7% of all malignant ovarian neoplasms, are unknown. Amplification and/or overexpression of the ERBB genes are a feature of many cancer types, and overexpression of erbB2 correlates with poor prognos...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-05-01 00:00:00
abstract::In the diagnosis of non-Hodgkin's lymphomas, the ready characterization of the neoplastic cell lineage by analysis of cell surface markers is of great importance. We present evidence for the existence of a human B-leukemia-associated antigen recognized by a complement-fixing monoclonal antibody (anti-Y 29/55). A hybri...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-05-01 00:00:00
abstract::Fatty acid synthase (FASN) is the terminal enzyme in de novo lipogenesis and plays a key role in cell proliferation. Pharmacologic inhibitors of FASN are being evaluated in clinical trials for treatment of cancer, obesity, and other diseases. Here, we report a previously unknown mechanism of FASN regulation involving ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-1597
更新日期:2016-12-01 00:00:00
abstract::This study was undertaken to examine relationships of the phenotype of malignant cells to target cell properties and to events early in the transformation process. Eighteen transformed lines were obtained by Kirsten murine sarcoma virus infection of cells from adrenal glands of rats ages 4 to 30 weeks, at first or sec...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-05-01 00:00:00
abstract::This study investigates the possible molecular basis leading to failure in a treatment that is composed of hypoxia and chemotherapy in a rat orthotopic hepatoma model. Hypoxia was induced by hepatic artery ligation, whereas chemotherapeutic effect was achieved by intraportal injection of cisplatin. High-dose sodium sa...
journal_title:Cancer research
pub_type: 杂志文章,收录出版
doi:10.1158/0008-5472.CAN-03-3311
更新日期:2004-08-01 00:00:00
abstract::Selectins bind to carbohydrate ligands in a calcium-dependent manner and play critical roles in host defense and possibly in tumor metastasis. To isolate peptides that mimic E-selectin ligands, we screened a phage peptide library using E-selectin as a target molecule. This attempt unexpectedly failed, probably because...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-01-15 00:00:00
abstract::In previous studies, we have demonstrated that transferrin-gallium inhibits cellular proliferation by a mechanism whereby cellular iron utilization is impaired. Since indium, a similar class 3A metal, has not been well studied, we examined its effects on cellular iron uptake and cellular proliferation. In these studie...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-08-01 00:00:00
abstract::Lymphomas are rarely, if ever, found to be in excess following exposure to ionizing radiation. Hodgkin's disease has never been linked to radiation, and the evidence for non-Hodgkin's lymphoma (NHL) is very weak. Low doses of radiation from diagnostic X-ray procedures or from occupational exposures do not appear to ca...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:
更新日期:1992-10-01 00:00:00
abstract::alpha(v)beta(3) integrin was investigated in multiple myeloma in relation to the in vitro osteoclast-like activity of malignant plasma cells. Myeloma cells from patients with skeleton involvement overexpressed alpha(v)beta(3) and produced erosion pits on bone substrates, whereas this effect was not observed by cells f...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-09-0949
更新日期:2009-08-15 00:00:00
abstract::In the first Phase I clinical trials of endostatin as an antiangiogenic therapy for cancer, the protein was administered as an i.v. bolus for approximately 20-30 min each day. This protocol was based on experimental studies in which animals were treated by s.c. bolus once a day. However, it was not clear in the previo...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-10-15 00:00:00
abstract::Morris 7777 hepatoma cells, maintained in culture for 5 days in Lewis medium supplemented with 0.1 to 0.35 mM cis-unsaturated fatty acid of the oleic (number of carbon atoms: number of double bonds, 18:1), linoleic (18:2), or arachidonic (20:4) type, were compared to similarly maintained, unsupplemented cells as to ul...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-11-01 00:00:00
abstract::The exposure of rats to a feeding regimen containing N-2-acetylaminofluorene (2AAF) causes an accumulation of lesions on liver DNA and a progressive impairment in DNA repair capacity. We used the in vivo experimental model of Teebor and Becker (Cancer Res., 31:1-3, 1971) with the carcinogen given to rats during four c...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-07-01 00:00:00
abstract::Between June 1977 and December 1979, 72 evaluable patients with childhood non-T-cell acute lymphoblastic leukemia were induced into complete remission using vincristine, prednisone, and doxorubicin. All received asparaginase consolidation and central nervous system prophylaxis with cranial irradiation and intrathecal ...
journal_title:Cancer research
pub_type: 临床试验,杂志文章,随机对照试验
doi:
更新日期:1983-11-01 00:00:00
abstract::Previous molecular analyses of human astrocytomas have identified many genetic changes associated with astrocytoma formation and progression. In an effort to identify novel gene expression changes associated with astrocytoma formation, which might reveal new potential targets for glioma therapeutic drug design, we use...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-06-01 00:00:00
abstract::The transplantable hormone-responsive rat mammary adenocarcinoma 13762NF was dissociated with collagenase and hyaluronidase. Cells were cloned directly or lines were established from mass cultures and cells from these lines were cloned. Clones differed in cellular morphology, colony morphology on plastic or in collage...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-04-01 00:00:00