Abstract:
:Although mutated forms of ras are not associated with the majority of breast cancers (<5%), there is considerable experimental evidence that hyperactive Ras can promote breast cancer growth and development. Therefore, we determined whether Ras and Ras-responsive signaling pathways were activated persistently in nine widely studied human breast cancer cell lines. Although only two of the lines harbor mutationally activated ras, we found that five of nine breast cancer cell lines showed elevated active Ras-GTP levels that may be due, in part, to HER2 activation. Unexpectedly, activation of two key Ras effector pathways, the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase and phosphatidylinositol 3'-kinase/AKT signaling pathways, was not always associated with Ras activation. Ras activation also did not correlate with invasion or the expression of proteins associated with tumor cell invasion (estrogen receptor alpha and cyclooxygenase 2). We then examined the role of Ras signaling in mediating resistance to matrix deprivation-induced apoptosis (anoikis). Surprisingly, we found that ERK and phosphatidylinositol 3'-kinase/AKT activation did not have significant roles in conferring anoikis resistance. Taken together, these observations show that Ras signaling exhibits significant cell context variations and that other effector pathways may be important for Ras-mediated oncogenesis, as well as for anoikis resistance, in breast cancer. Additionally, because ERK and AKT activation are not strictly associated with Ras activation, pharmacological inhibitors of these two signaling pathways may not be the best approach for inhibition of aberrant Ras function in breast cancer treatment.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Eckert LB,Repasky GA,Ulkü AS,McFall A,Zhou H,Sartor CI,Der CJdoi
10.1158/0008-5472.CAN-04-0396subject
Has Abstractpub_date
2004-07-01 00:00:00pages
4585-92issue
13eissn
0008-5472issn
1538-7445pii
64/13/4585journal_volume
64pub_type
杂志文章相关文献
CANCER RESEARCH文献大全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::verapamil, a calcium-influx blocker, enhanced the cytotoxicity of vincristine (VCR) in vitro 6- to 12-fold in eight human hemopoietic tumor cell lines established from acute lymphatic leukemia, acute myelogenous leukemia, and Burkitt's lymphoma. Great enhancement of VCR cytotoxicity was obtained in a VCR-resistant sub...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-05-01 00:00:00
abstract::The treatment of glioblastoma (GBM) remains challenging in part due to the presence of stem-like tumor-propagating cells that are resistant to standard therapies consisting of radiation and temozolomide. Among the novel and targeted agents under evaluation for the treatment of GBM are BRAF/MAPK inhibitors, but their e...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-14-3689
更新日期:2015-12-15 00:00:00
abstract::It is fairly well accepted that the presence of estrogen receptor (ER) and progesterone receptor (PgR) identifies breast cancer patients with a lower risk of relapse and better overall survival. But patients with discordant receptors, the ER+/PgR- phenotype, are often intermediate in clinical response. We focused upon...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-01-15 00:00:00
abstract::The XC infectious center assay was used to study the nature of the lymphoid cells producing N-tropic C-type viruses in preleukemic AKR mice. Viral production by thymic cell suspensions was very low and was possibly due to contaminating cells. Production at least 100-fold higher was found in spleen cells and was probab...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1978-04-01 00:00:00
abstract::The recent identification of cancer stem cells (CSCs) in multiple human cancers provides a new inroad to understanding tumorigenesis at the cellular level. CSCs are defined by their characteristics of self-renewal, multipotentiality, and tumor initiation upon transplantation. By testing for these defining characterist...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-0786
更新日期:2008-12-15 00:00:00
abstract::A series of nitrofuran-based compounds were identified as inhibitors of estrogen signaling in a cell-based, high-throughput screen of a diverse library of small molecules. These highly related compounds were subsequently found to inhibit topoisomerase II in vitro at concentrations similar to that required for the inhi...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-0393
更新日期:2007-05-01 00:00:00
abstract::Drug sensitivity assays were performed using a variation of a colorimetric [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT)] assay on V79, CHO-AuxB1, CHRC5, NCI-H460, and NCI-H249 cell lines following optimization of experimental conditions for each cell line. Results from this assay were compared w...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-02-15 00:00:00
abstract::Fractalkine is a CX3C-type chemokine that induces chemotaxis of monocytes and cytotoxic T cells. Using the differential display method for examining gene expression in p53-defective cells transfected by adenovirus containing wild-type p53, we observed that fractalkine was induced by ectopic expression of p53. An elect...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-07-15 00:00:00
abstract::Fibroblast growth factor (FGF) receptor (FGFR) substrate 2 (FRS2) is an adaptor protein that plays a critical role in FGFR signaling. FRS2 is located on chromosome 12q13-15 that is frequently amplified in liposarcomas. The significance of FRS2 and FGFR signaling in high-grade liposarcomas is unknown. Herein, we first ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-12-2086
更新日期:2013-02-15 00:00:00
abstract::The Salmonella-microsome assay for mutagenesis was used to determine the effect of ozone on the mutagenesis of selected carcinogens and mutagens in water. Short periods of ozonation were shown to completely inactivate the mutagenicity of several polyaromatic amine mutagens including acriflavine, proflavine, and beta-n...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-06-01 00:00:00
abstract::An increased level of chondroitin sulfate (CS) expression on the cell surface is often associated with malignant transformation and the progression of tumor cells. In this study, CSs expressed on highly metastatic tumor cells were used as a target for the selective delivery of anticancer drugs by polyethylene glycol (...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-08-01 00:00:00
abstract::MCT-1 is an oncogene that was initially identified in a human T cell lymphoma and has been shown to induce cell proliferation as well as activate survival-related pathways. MCT-1 contains the PUA domain, a recently described RNA-binding domain that is found in several tRNA and rRNA modification enzymes. Here, we estab...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-1999
更新日期:2006-09-15 00:00:00
abstract::The pathogenetic relationship between high-grade prostatic intraepithelial neoplasia (PIN), prostatic carcinoma, and metastases is poorly understood. We used fluorescence in situ hybridization (FISH) with centromere-specific probes for chromosomes 7, 8, 10, 12, and Y to evaluate numeric chromosomal anomalies in PIN (6...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1995-11-15 00:00:00
abstract::For many solid tumors, surgical resection remains the gold standard and tumor-involved margins are associated with poor clinical outcomes. Near-infrared (NIR) fluorescence imaging using molecular agents has shown promise for in situ imaging during resection. However, for cancers with difficult imaging conditions, surg...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-0878
更新日期:2018-09-01 00:00:00
abstract::Acinetobacter glutaminase-asparaginase (AGA) and Escherichia coli asparaginase were compared for their effects on plasma and tissue levels of amino acids, ammonia, and glutamyl transferase activity in the mouse. Free asparagine was depleted similarly in plasma and tissues by both enzymes. AGA treatment produced partia...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-05-01 00:00:00
abstract::Patients with disseminated Ewing's family of tumors (ESFT) often experience drug-resistant relapse. We hypothesize that targeting minimal residual disease with the cytotoxic retinoid N-(4-hydroxyphenyl) retinamide (4-HPR; fenretinide) may decrease relapse. We determined the following: (a) 4-HPR cytotoxicity against 12...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-04-0377
更新日期:2004-08-01 00:00:00
abstract::The chemokine receptor, CXCR4, is expressed by human melanomas, and its ligand, CXCL12, is frequently produced at sites of melanoma metastasis. Herein, we examine CXCR4-enhanced binding of B16 murine melanoma cells to endothelial cells (ECs) and recombinant adhesion molecules in vitro to determine the role of tumor- a...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-10-15 00:00:00
abstract::An approach to stimulating an immune response against tumors is to transduce tumor cells with bacterial genes, which represent a "danger signal" and can induce a wide immune response. Mycobacterium tuberculosis genes and their encoded proteins play a pivotal role in linking innate and cell-mediated adaptive immunity a...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-07-15 00:00:00
abstract::Non-P-glycoprotein multidrug resistance of HL60/ADR cells appears to be related to overexpression of the MRP gene. Recent studies suggest that this gene may play an important role in a new form of cell resistance to certain chemotherapeutic agents. To examine mechanisms regulating transcriptional activity of this gene...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-08-15 00:00:00
abstract::Isolated mitochondria from highly glycolytic Ehrlich and AS30-D tumor cells have a 12.4- and a 2.3-fold higher cholesterol level, respectively, than that of rat liver mitochondria. The passive proton permeability of Ehrlich and AS30-D tumor inner membrane mitochondria is, respectively, 4- and 1.4-fold lower than that ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-09-15 00:00:00
abstract::Low-density lipoprotein (LDL) could be used as a carrier of chemotherapeutic agents to neoplastic cells that overexpress LDL receptors (rLDL), but LDL is difficult to obtain and handle. Recently, it was observed that a protein-free emulsion resembling the lipid portion of LDL (LDE) behave like native LDL when injected...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-09-01 00:00:00
abstract::Two newly synthesized nitrosoureido sugars have been evaluated for their antitumor activity and diabetogenic potential in a number of in vitro and in vivo preclinical tumor model systems. 2-Amino-2-deoxy-N'-methyl-N'-nitrosoureido-1,3,4,6-tetra-O-acetyl-alpha- D- mannopyranose (MAZ), a lipophilic mannosamine derivativ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::The influence of cyclophosphamide (CY) on Friend virus leukemogenesis was studied in SJL/J, C57BL/10J, and C57BL/10J X SJL/J F1 (hereafter called B10SJF1) mice. All three differ in their susceptibility to the viral oncogenic effect. Immunosuppressive doses of CY, which by themselves produced no cancer, were followed 2...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::Hypoxia initiates numerous intracellular signaling pathways important in regulating cell proliferation, differentiation, and death. In this study, we investigated the pathway that hypoxia uses to activate Akt and inactivate glycogen synthase kinase-3 (GSK-3), two proteins the functions of which are important in cell s...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-03-15 00:00:00
abstract::A patient presented with a primary melanoma, Level IV, 2.5 mm thick; 30 excised lymph nodes were all negative for tumor. Four local recurrences followed in the ensuing 17 months. Tumor cells cultured at this time were epithelioid. Autoimmunization was followed by a disease-free interval of 15 months. Postimmunization,...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-07-01 00:00:00
abstract::The rate of repopulation of surviving cells increases during fractionated radiotherapy and limits the ability to control tumors. Repopulation is likely to be more important during the longer intervals between courses of chemotherapy and is a potential cause of clinical resistance to chemotherapy. To evaluate the rate ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2003-05-01 00:00:00
abstract::Epithelial to mesenchymal transition occurs during embryologic development to allow tissue remodeling and is proposed to be a key step in the metastasis of epithelial-derived tumors. The miR-200 family of microRNAs plays a major role in specifying the epithelial phenotype by preventing expression of the transcription ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-1942
更新日期:2008-10-01 00:00:00
abstract::Myeloid-derived suppressor cells (MDSC) are a heterogeneous group of immature myeloid cells that expand in tumor-bearing hosts in response to soluble factors produced by tumor and stromal cells. MDSC expansion has been linked to loss of immune effector cell function and reduced efficacy of immune-based cancer therapie...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-1490
更新日期:2016-04-15 00:00:00
abstract::Cloning efficiencies of 67 fresh human tumor specimens, consisting of 29 ovarian, 10 lung, and 7 each of colon, breast, mesenchymal, and miscellaneous tumors, from 58 patients were studied using the technique of Hamburger and Salmon to evaluate the effect of incubation in a 5% rather than 20% oxygen environment. Under...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-10-01 00:00:00