Abstract:
:Loss of susceptibility to apoptosis signals is a crucial step in carcinogenesis. Therefore, sensitization of tumor cells to apoptosis is a promising therapeutic strategy. c-Jun-N-terminal-kinases (JNK) have been implicated in stress-induced apoptosis, but may also contribute to survival signaling. Here we show that CD95-induced apoptosis is augmented by the JNK inhibitor SP600125 and small interfering RNA directed against JNK1/2. SP600125 potently inhibited methyl methane sulfonate-induced phosphorylation of c-Jun, but had minimal effect on apoptosis alone. In contrast, it strongly enhanced CD95-mediated apoptosis in six of eight tumor cell lines and led to a G2/M phase arrest in all cell lines. SP600125 enhanced cleavage of caspase 3 and caspase 8, the most upstream caspase in the CD95 pathway. JNK inhibition up-regulates p53 and its target genes p21Cip1/Waf1 and CD95. However, although HCT116 p53-/- cells and p21+/+ cells were less sensitive to CD95 stimulation than their p53+/+ and p21-/- counterparts, p53 and p21 were not involved in the JNK-mediated effect. JunD, which was described to be protective in tumor necrosis factor-induced apoptosis, was not regulated by JNK inhibition on the protein level. When transcription was blocked by actinomycin D, JNK inhibition still enhanced apoptosis to a comparable extent. We conclude that JNK inhibition has antitumor activity by inducing growth arrest and enhancing CD95-mediated apoptosis by a transcription-independent mechanism.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Kuntzen C,Sonuc N,De Toni EN,Opelz C,Mucha SR,Gerbes AL,Eichhorst STdoi
10.1158/0008-5472.CAN-04-2618subject
Has Abstractpub_date
2005-08-01 00:00:00pages
6780-8issue
15eissn
0008-5472issn
1538-7445pii
65/15/6780journal_volume
65pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract::Three Burkitt's lymphoma cell lines were studied for their response to cis-diamminedichloroplatinum(II) (cis-DDP) and L-phenylalanine mustard (L-PAM) with the objective of relating cytotoxicity to DNA cross-linking in human cells. Cytotoxicity was measured by cell proliferation and colony formation assays. DNA interst...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-03-01 00:00:00
abstract::A purse-string suture was put into the rat's cecum to form a "diverticulum." When the thread cut this stitch, the resultant extensive necrotic zone healed for a long time. The presence of a foreign body (ligature) provided a permanent source of injury to the cecal mucosa. The lesions caused an increase in [3H]thymidin...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1975-12-01 00:00:00
abstract::We have analyzed the mechanism of activation of two human ras oncogenes. We have also identified a rasN gene from a human gastric adenocarcinoma which efficiently induced both morphological transformation and tumorigenicity of NIH3T3 cells in a transfection assay. The rasN gene in tumor tissue DNA did not appear to be...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-09-01 00:00:00
abstract::The metabolism of the rat esophageal carcinogen N-nitrosomethylbenzylamine (NMBzA) was studied using microsomes prepared from liver and esophageal mucosa of untreated male Sprague-Dawley rats. NMBzA was extensively metabolized to benzaldehyde, benzyl alcohol, and formaldehyde by hepatic microsomes. The rate of metabol...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1982-08-01 00:00:00
abstract::Ewing's sarcoma is thought to arise after developmental arrest of primitive neural cells during embryogenesis. Because basic fibroblast growth factor (bFGF) has a critical role in the regulation of cell survival, proliferation, and differentiation during embryogenesis, we have tested the hypothesis that bFGF and FGF r...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2000-11-01 00:00:00
abstract::Breast cancers expressing estrogen receptor-alpha (ERalpha) are associated with a favorable biology and are more likely to respond to hormonal therapy. In addition to ERalpha, other pathways of estrogen response have been identified including ERbeta and GPR30, a membrane receptor for estrogen, and the key mechanisms r...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-07-2293
更新日期:2007-09-15 00:00:00
abstract::Membrane-type matrix metalloproteinases (MT-MMP) constitute a subfamily of six distinct membrane-associated MMPs. Although the contribution of MT1-MMP during different steps of cancer progression has been well documented, the significance of other MT-MMPs is rather unknown. We have investigated the involvement of MT4-...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-3012
更新日期:2006-05-15 00:00:00
abstract::Normal bone marrow progenitors and some leukemic cells develop only a limited amount of thermotolerance. Further, once developed, thermotolerance decays at a faster rate than that normally observed in cells of nonhemopoietic origin. Thermotolerance induction and maintenance correlates with reduced levels of expression...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1992-12-15 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::The long-term effects on mammary glands of 5beta-dihydrotestosterone, considered to be biologically inactive, were studied in female SHN mice with mammary tumor, virus. 5beta-Dihydrotestosterone was adminstered to mothers for 4 days from Day 12 to Day 15 of pregnancy (prenatal treatment) and to pups for 5 days of post...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1977-12-01 00:00:00
abstract::During a 2-yr study of carcinogenesis by CdCl2 in male Wistar [Crl:(WI)BR] rats, weekly clinical observations during the last 6 mo of the study revealed many cases of persistent tumor-like masses at the site of the metal identification tags in the ears of the animals. A total of 14 tumors (mostly compound osteosarcoma...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1987-05-01 00:00:00
abstract::Adult female rat urinary bladders were exposed to N-methyl-N-nitrosourea in vivo. After 12 weeks, urothelial hyperplasia was established. Ultrastructural changes of the luminal plasma membrane were studied with thin sectioning and freeze-fracturing techniques. The mosaic pattern which is a characteristic specializatio...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1979-09-01 00:00:00
abstract::An anemia-inducing substance was isolated from the human placenta and designated placental anemia-inducing factor (PAIF). An amount of 2.8 mg was purified from about 70 total placentas (total wet weight, 42 kg). PAIF caused hemolysis of human erythrocytes in vitro and reduced the number of erythrocytes in rabbits to 8...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1980-05-01 00:00:00
abstract::Epidemiological data have provided clues to the etiological factors involved in large bowel cancer development. High intake of dietary fat tends to promote colon carcinogenesis. Studies in metabolic epidemiology have shown that the high dietary fat affects the metabolic activity of gut bacteria as well as the levels o...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1981-09-01 00:00:00
abstract::Sarcoma growth factor (SGF) induces proliferation and anchorage-independent growth of nonmalignant cells. It competes with epidermal growth factor (EGF) for the EGF-receptors at the cell surface. SGF-like factors have recently been isolated from embryos, suggesting that SGFs may represent embryonic forms of EGF. There...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1983-12-01 00:00:00
abstract::Blood vessels deliver oxygen and nutrients to tissues, and vascular networks are spatially organized to meet the metabolic needs for maintaining homeostasis. In contrast, the vasculature of tumors is immature and leaky, resulting in insufficient delivery of nutrients and oxygen. Vasculogenic processes occur normally i...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-10-0412
更新日期:2010-08-01 00:00:00
abstract::We observed that photodynamic therapy (PDT) induces the expression and phosphorylation of the inhibitor of apoptosis (IAP) protein survivin in murine and human cancer cells and tumors. Survivin inhibits caspase-9, blocks apoptosis, and is associated with resistance to chemotherapy and radiation. Survivin is a client p...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-06-4785
更新日期:2007-05-15 00:00:00
abstract::Telomerase is a ribonucleoprotein that synthesizes telomeric DNA on chromosomal ends. Telomerase activation has been seen in many immortal cell lines and cancers. Telomerase activity was analyzed in prostate carcinoma; in coexistent prostatic intraepithelial neoplasia (PIN), benign prostatic hyperplasia (BPH), atrophy...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1998-02-15 00:00:00
abstract::Telomerase is essential for immortalization of most human cancer cells. Expression of the core telomerase RNA (hTR) and reverse transcriptase (hTERT) subunits is mainly regulated by transcription. However, hTR transcriptional regulation remains poorly understood. We previously showed that the core hTR promoter is acti...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-05-1941
更新日期:2006-02-01 00:00:00
abstract::Interleukin-2-based regimens of biological therapy have shown some clinical promise for the treatment of kidney cancer in humans, although the mechanisms responsible for tumor regression occurring in these patients remain unclear. Preclinical insight into these mechanisms is limited by a paucity of orthotopic animal m...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:2001-08-15 00:00:00
abstract::PD115934 (NSC 366140) is a soluble pyrazoloacridine derivative presently undergoing preclinical toxicology evaluation with the anticipation of Phase I human investigation. The agent displayed both human and murine solid tumor selectivity in vitro in a soft agar disk diffusion assay, relative to its activity against mu...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1990-08-15 00:00:00
abstract::Purines were long thought to be restricted to the intracellular compartment, where they are used for energy transactions, nucleic acid synthesis, and a multiplicity of biochemical reactions. However, it is now clear that both adenosine and adenosine triphosphate are (i) abundant biochemical components of the tumor mic...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-12-1600
更新日期:2012-11-01 00:00:00
abstract::Chloroethylnitrosoureas (CNUs) are being used in the therapy of various neoplastic diseases, including skin cancer. Because secondary tumor formation is a serious threat in chemotherapy with these drugs, we explored whether and to what extent the DNA repair protein DNA-O6-methylguanine:protein-L-cysteine S-methyltrans...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1997-08-15 00:00:00
abstract::Immune checkpoint therapies exhibit impressive efficacy in some patients with melanoma or lung cancer, but the lack of response in most cases presses the question of how general efficacy can be improved. In addressing this question, we generated a preclinical tumor model to study anti-PD-1 resistance by in vivo passag...
journal_title:Cancer research
pub_type: 杂志文章
doi:10.1158/0008-5472.CAN-15-3142
更新日期:2017-02-15 00:00:00
abstract::Aberrant methylation patterns have long been known to exist in the promoter regions of key regulatory genes in the DNA of tumor cells. However, the mechanisms by which these methylation patterns become altered during the transformation of normal cells to tumor cells have remained elusive. We have recently shown in in ...
journal_title:Cancer research
pub_type: 杂志文章,评审
doi:10.1158/0008-5472.CAN-07-0846
更新日期:2007-06-15 00:00:00
abstract::The specific delivery of radioisotopes to a tumor at minimal radiation of normal tissue is the ultimate aim of radioimmunotherapy. In this respect a two-step pretargeting regimen generally leads to an improved tumor to normal tissue uptake ratio compared to direct administration of radioimmunoconjugates. In this paper...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1994-07-01 00:00:00
abstract::The effect of intragastric gavage administration of docosahexaenoic acid (DHA) on the formation of 1,2-dimethylhydrazine (DMH)-induced aberrant crypt foci in rat colon was investigated. Male F344 rats were treated three times s.c. with 20 mg/kg of DMH and were given either 0.7 ml of DHA or water intragastrically 5 tim...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-06-15 00:00:00
abstract::Experimental studies using murine tumor models have demonstrated that potent systemic immunity can be generated using tumor vaccines engineered by gene transfer to secrete certain cytokines. The underlying physiological principle behind these strategies involves the sustained release of high doses of cytokine at the s...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1993-12-15 00:00:00
abstract::We have previously shown that mice simultaneously infected with the murine mammary tumor virus (MuMTV) and with certain slow murine leukemia viruses (MLV) have an increased resistance to the pathological effects of both agents. Here we report that milk-transmitted MuMTV also delays the development of the acute erythro...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1986-08-01 00:00:00
abstract::A recently developed non-ionic surfactant called Solutol HS 15 (poly-oxyethylene esters of 12-hydroxystearic acid), with low toxicity in vivo, was shown to reverse completely the multidrug resistance of KB 8-5 and KB 8-5-11 human epidermoid carcinoma cells in vitro but did not potentiate drug toxicity in drug-sensitiv...
journal_title:Cancer research
pub_type: 杂志文章
doi:
更新日期:1991-02-01 00:00:00