Abstract:
:Nitric oxide (NO) in nanomolar (nmol/L) concentrations is consistently detected in tumor microenvironment and has been found to promote tumorigenesis. The mechanism by which NO enhances tumor progression is largely unknown. In this study, we investigated the possible mechanisms and identified cellular targets by which NO increases proliferation of human breast cancer cell lines MDA-MB-231 and MCF-7. DETA-NONOate, a long acting NO donor, with a half-life of 20 h, was used. We found that NO (nmol/L) dramatically increased total protein synthesis in MDA-MB-231 and MCF-7 and also increased cell proliferation. NO specifically increased the translation of cyclin D1 and ornithine decarboxylase (ODC) without altering their mRNA levels or half-lives. Critical components in the translational machinery, such as phosphorylated mammalian target of rapamycin (mTOR) and its downstream targets, phosphorylated eukaryotic translation initiation factor and p70 S6 kinase, were up-regulated following NO treatment, and inhibition of mTOR with rapamycin attenuated NO induced increase of cyclin D1 and ODC. Activation of translational machinery was mediated by NO-induced up-regulation of the Raf/mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase/ERK (Raf/MEK/ERK) and phosphatidylinositol 3-kinase (PI-3 kinase)/Akt signaling pathways. Up-regulation of the Raf/MEK/ERK and PI-3 kinase/Akt pathways by NO was found to be mediated by activation of Ras, which was cyclic guanosine 3',5'-monophosphate independent. Furthermore, inactivation of Ras by farnesyl transferase inhibitor or K-Ras small interfering RNA attenuated NO-induced increase in proliferation signaling and cyclin D1 and ODC translation, further confirming the involvement of Ras activation during NO-induced cell proliferation.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Pervin S,Singh R,Hernandez E,Wu G,Chaudhuri Gdoi
10.1158/0008-5472.CAN-05-4623subject
Has Abstractpub_date
2007-01-01 00:00:00pages
289-99issue
1eissn
0008-5472issn
1538-7445pii
67/1/289journal_volume
67pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::A rapid method for the measurement of serum and/or plasma, lipid-associated sialic acid levels has been developed. This test has been applied to 850 human sera of which 670 came from patients with nine categories of malignant disease, 80 from persons with benign disorders, and 100 from normal individuals. Lipid-associ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-12-01 00:00:00
abstract::Preliminary results from a pilot trial on trastuzumab's mechanism of action against operable breast tumors overexpressing Her2 suggested a role for antibody-dependent cell cytotoxicity (ADCC). To examine factors affecting ADCC intensity and variability, we extended this study to the phenotypic and functional analysis ...
journal_title:Cancer research
pub_type: 临床试验,杂志文章
doi:10.1158/0008-5472.CAN-07-2068
更新日期:2007-12-15 00:00:00
abstract::Thymidine phosphorylase (dThdPase)/platelet-derived endothelial cell growth factor is expressed at higher levels in a variety of human carcinomas than it is in adjacent normal tissue. The higher expression is associated with an increase of intratumoral microvessel density (IMVD) and an unfavorable patient prognosis. W...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1999-10-01 00:00:00
abstract::Electron micrographs of CCL237 and FET cells (two slowly growing, differentiated human colon carcinoma lines) revealed enlarged mitochondria with few cristae. Polarographic measurement of respiratory activity in mitochondria isolated from these cell lines was compared to that of CV-1 cells (a normal monkey kidney epit...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-06-15 00:00:00
abstract::An orthotopic human lung cancer model in nu/nu mice was used to study the effect of an antisense K-ras (AS-K-ras) retroviral construct on tumor growth in vivo. A 2-kilobase genomic AS-K-ras DNA fragment linked to a beta-actin promoter was cloned into the LNSX retroviral vector. The recombinant construct was packaged i...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-04-15 00:00:00
abstract::Three groups of 6 to 8-week-old male mice with transplanted C57BL/6 X DBA/2F1 tumor were irradiated by a single dose of 60Co localized on the tumor in association with i.p. injections of lyophilized Bacillus Calmette-Guérin. When the animals were sacrificed, tumor parameters (weight, surface area, and volume) were det...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-05-01 00:00:00
abstract::Although numerous studies have implicated vitamin D in preventing prostate cancer, the underlying mechanism(s) remains unclear. Using normal human prostatic epithelial cells, we examined the role of mitogen-activated protein kinase phosphatase 5 (MKP5) in mediating cancer preventive activities of vitamin D. Up-regulat...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-3796
更新日期:2006-04-15 00:00:00
abstract::Using in vitro double labeling with two different doses of [3H]thymidine, we measured the S-phase duration and the labeling index in biopsy samples taken from human rectal and colonic adenocarcinomas. Samples from the adjacent healthy mucosa, taken at the same time as the tumor samples, were simultaneously subjected t...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1976-02-01 00:00:00
abstract::Solid tumors have a heterogeneous pathophysiology, which directly affects antibody-targeted therapies. Here, we consider the influence of selected tumor parameters on radioimmunotherapy, by comparing the gross biodistribution, microdistribution, and therapeutic efficacy of either radiolabeled or fluorescently labeled ...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-2967
更新日期:2007-12-15 00:00:00
abstract::A total of 224 chemicals that have been tested in long-term studies for carcinogenicity in rats and mice by the National Cancer Institute and the National Toxicology Program were tested for mutagenicity in Salmonella typhimurium. Correlations between mutagenicity and carcinogenicity were examined. The influences of ch...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-03-01 00:00:00
abstract::Oligodendrogliomas are a specific subtype of brain tumor of which the majority responds favorably to chemotherapy. In this study, we made use of expression profiling to identify chemosensitive oligodendroglial tumors. Correlation of expression profiles to loss of heterozygosity on 1p and 19q, common chromosomal aberra...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-1886
更新日期:2005-12-15 00:00:00
abstract::Loss of expression of the E-cadherin cell-cell adhesion molecule is important in carcinoma development and progression. Because previous data suggest that loss of E-cadherin expression in breast carcinoma may result from a dominant transcriptional repression pathway acting on the E-cadherin proximal promoter, we pursu...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2002-03-15 00:00:00
abstract::Constitutively active RAS small GTPases promote the genesis of human cancers. An important goal in cancer biology is to identify means of countervailing activated RAS signaling to reverse malignant transformation. Oncogenic K-RAS mutations are found in virtually all pancreatic adenocarcinomas, making the RAS pathway a...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-4471
更新日期:2007-12-15 00:00:00
abstract::Monoclonal antibodies (MAbs) targeted to glioma-associated antigens may allow the selective delivery of imaging and therapeutic agents to brain tumors; the use of MAb fragments may be a strategy to further improve tumor uptake of such agents relative to normal tissues. In this study, we have examined the in vivo local...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1988-10-15 00:00:00
abstract::Understanding the intratumoral heterogeneity of hepatocellular carcinoma is instructive for developing personalized therapy and identifying molecular biomarkers. Here we applied whole-exome sequencing to 69 samples from 11 patients to resolve the genetic architecture of subclonal diversification. Spatial genomic diver...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-16-2822
更新日期:2017-05-01 00:00:00
abstract::The potential to heighten the efficacy of antiangiogenic agents was explored in this study based on active targeting of tumor cells overexpressing the gonadotropin-releasing hormone receptor (GnRH-R). The rational design pursued focused on five analogues of a clinically established antiangiogenic compound (sunitinib),...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-2138
更新日期:2016-03-01 00:00:00
abstract::The radionuclide of choice for use in diagnosis in most nuclear medicine diagnostic procedures is 99mTc. It is important, therefore, to establish whether there is potential clinical efficacy of an antitumor antigen directed monoclonal antibody labeled with 99mTc. We have investigated the potential use of a 99mTc label...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-02-01 00:00:00
abstract::MRI is the gold standard for confirming a pelvic lymph node metastasis diagnosis. Traditionally, medical radiologists have analyzed MRI image features of regional lymph nodes to make diagnostic decisions based on their subjective experience; this diagnosis lacks objectivity and accuracy. This study trained a faster re...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-0494
更新日期:2018-09-01 00:00:00
abstract::Human B-cell tumors have been established in athymic, BALB/c mice using the EBV-positive Burkitt lymphoma cell line Namalwa. One-hundred-one of 104 animals (97%) developed tumors 10-14 days following s.c. injection of a mixture of 20 x 10(6) Namalwa and 5 X 10(6) irradiated human fibrosarcoma (HT-1080) cells. Tumors d...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-06-01 00:00:00
abstract::Many but not all of the cell surface antigens studied were released into tissue culture medium of human colorectal carcinoma and melanoma cells maintained in vitro. Two groups of monoclonal antibody-defined antigens are described. One group is composed of molecules that are released easily and in large quantitites int...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-07-01 00:00:00
abstract::Three mouse monoclonal antibodies to distinct cell surface antigens were derived from immunizations with cells of Tera-1, a human teratocarcinoma cell line, and a membrane preparation of placental tissue. The distribution of the antigens on 165 cultured lines of various human tumors and normal cells was determined by ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-02-01 00:00:00
abstract::There is little information on early molecular events in the development of N-nitrosomethylbenzylamine (NMBA)-induced rat esophageal tumorigenesis and of the effects of chemopreventive agents on these events. In this study, we identified genes in rat esophagus that were differentially expressed in response to short-te...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-4531
更新日期:2007-07-01 00:00:00
abstract::Studies involving transcriptomics have revealed multiple molecular subtypes of hepatocellular carcinoma (HCC). Positron emission tomography/computed tomography (PET/CT) has also identified distinct molecular imaging subtypes, including those with increased and decreased choline metabolism as measured by the tissue upt...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-18-3837
更新日期:2019-04-01 00:00:00
abstract::Two populations of nuclear androgen receptors have been characterized in human prostatic tissue, and the levels and proportions of each were found to differ in normal prostates, benign hyperplastic prostates (BPH), and malignant prostates. A significant percentage (35 to 50%) of total nuclear androgen receptors was as...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-03-01 00:00:00
abstract::It has long been known that complex interactions occur between tumors and normal host immune cells. The human melanoma cell line A375 has been used previously as an indicator cell for tumor cell cytotoxicity mediated by monocytes. During other studies on this tumor cell line, we noted that the conditioned media harves...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-05-01 00:00:00
abstract::Adenocarcinoma of the rete testis is an exceptionally rare and malignant testicular neoplasm. Although treatment of pregnant women with diethylstilbestrol (DES) results in reproductive tract abnormalities in their male offspring, increased incidence of testicular tumors has not been verified. However, recently three c...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1985-10-01 00:00:00
abstract::Quantitation of D-beta-hydroxybutyrate dehydrogenase (BDH) in normal rat hepatocytes was compared with that in two rat hepatoma cell lines, H4-II-EC3 and RLT-3C. BDH activity in normal rat hepatocyte mitochondria was 321 nmol/min/mg, which was greatly reduced to 10.7 nmol/min/mg and 1.7 nmol/min/mg in H4-II-EC3 and RL...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1989-05-01 00:00:00
abstract::TGF-β has limited effects on ovarian cancer cells, but its contributions to ovarian tumor growth might be mediated through elements of the tumor microenvironment. In the present study, we tested the hypothesis that TGF modulates ovarian cancer progression by modulating the contribution of cancer-associated fibroblasts...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-13-0023
更新日期:2013-08-15 00:00:00
abstract::Factors affecting the expression of carcinoembryonic antigen (CEA) at the surface of in vitro human colon carcinoma cells were determined using 125I-labeled antibodies. Binding of specific anti-CEA antibodies resulted in polar redistribution of CEA, followed by endocytosis of most of the CEA-anti-CEA complexes. These ...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1980-12-01 00:00:00
abstract::Compelling evidences indicate a key role for regulatory T cells (T(reg)) on the host response to cancer. The Wilms' tumor antigen (WT1) is overexpressed in several human leukemias and thus considered as promising target for development of leukemia vaccine. However, recent studies indicated that the generation of effec...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-08-0050
更新日期:2008-08-01 00:00:00