Abstract：
:Receptor protein-tyrosine kinases (RPTKs) are tightly regulated during normal cellular processes including cell growth, differentiation, and metabolism. Recently, a RPTK-like molecule named novel oncogene with kinase-domain (NOK) has been cloned and characterized. Overexpression of NOK caused severe cellular transformation as well as tumorigenesis and metastasis in nude mice. In the current study, we generated two tyrosine-->phenylalanine (Y-->F) point mutations (Y327F and Y356F) within the endodomain of NOK that are well conserved in many RPTK subfamilies and are the potential tyrosine phosphorylation sites important for major intracellular signaling. Using BaF3 cells stably expressing the ectodomain of mouse erythropoietin receptor, and the transmembrane and endodomain of NOK (BaF3-E/N), we were able to show that point mutations at either Y327 or Y356 dramatically blocked cellular transformation by NOK as examined by colony formation and cellular DNA synthesis. In addition, tumorigenesis induced by BaF3-E/N was completely abrogated upon the introduction of either single mutation. Importantly, signaling studies revealed that the activation of extracellular signal-regulated kinase was inhibited by Y356F and was significantly reduced by Y327F. Both mutations significantly impaired Akt phosphorylation. Interestingly, both mutations did not affect the kinase activity of NOK. Moreover, apoptotic analysis revealed that both mutations accelerated cell death by activating caspase-3-mediated pathways. Thus, our study shows that these potential tyrosine phosphorylation sites may play critical roles in NOK-mediated tumorigenesis both in vitro and in vivo.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Chen Y,Li YH,Chen XP,Gong LM,Zhang SP,Chang ZJ,Zhang XF,Fu XY,Liu Ldoi
10.1158/0008-5472.CAN-05-1091subject
Has Abstractpub_date
2005-12-01 00:00:00pages
10838-46issue
23eissn
0008-5472issn
1538-7445pii
65/23/10838journal_volume
65pub_type
杂志文章相关文献
CANCER RESEARCH文献大全abstract：:We have produced a panel of monoclonal antibodies directed against a dimethylbenzanthracene-induced murine mammary tumor. Five rat-mouse hybridomas produced antibodies that bound to some murine mammary tumors, but not to normal renal adherent cells, lymphocytes, 3T3 fibroblasts, red blood cells, or mammary gland. One ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1985-08-01 00:00:00
abstract：:AS1411 is a first-in-class anticancer agent, currently in phase II clinical trials. It is a quadruplex-forming oligodeoxynucleotide that binds to nucleolin as an aptamer, but its mechanism of action is not completely understood. Mechanistic insights could lead to clinically useful markers for AS1411 response and to no...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-10-0920
更新日期：2010-11-01 00:00:00
abstract：:We showed recently that Helicobacter infection induces expression of cyclooxygenase-2 and microsomal prostaglandin E synthase-1 in the mouse stomach, and that transgenic mice expressing both cyclooxygenase-2 and microsomal prostaglandin E synthase-1 (K19-C2mE mice) develop hyperplastic gastric tumors with inflammatory...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-1936
更新日期：2005-10-15 00:00:00
abstract：:Cross-coupling of active protein-1 (AP-1) and nuclear factor (NF)-kappaB has been reported. In the present study, we investigated the possibility that both of these two transcription factors might contribute to the process of tumor promoter-induced transformation. To establish a stable reporter cell system, two report...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-08-15 00:00:00
abstract：:Antivascular therapy directed against VEGF or its receptors (VEGFR) has been successful when administered at early stages of tumor vessel growth but is less effective when administered later. Tumor blood vessels are heterogeneous, so vessel subpopulations may differ in their requirements for tumor cell-secreted VEGF a...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-11-1693
更新日期：2011-11-15 00:00:00
abstract：:Aneuploidy is invariably associated with poor proliferation of primary cells, but the specific contributions of abnormal karyotypes to cancer, a disease characterized by aneuploidy and dysregulated proliferation, remain unclear. In this study, I demonstrate that the transcriptional alterations caused by aneuploidy in ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-13-0749
更新日期：2013-11-01 00:00:00
abstract：:The majority of colorectal cancers have lost/inactivated the p53 tumor suppressor gene. Using isogenic human colon cancer cells that differ only in their p53 status, we demonstrate that loss of p53 renders tumor cells relatively resistant to the topoisomerase I inhibitor, irinotecan. Whereas irinotecan-induced up-regu...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-04-2488
更新日期：2004-12-15 00:00:00
abstract：:There have been few reported visual observations of metastatic cancer cell arrest in vivo. To seek evidence that inducible vascular adhesive properties can regulate hepatic metastasis, groups of 9-14 c57bl/6 mice were given 1.5 microg of interleukin-1alpha (IL-1alpha) 4 h before the injection of 3 x 10(5) B16F1 melano...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1997-09-15 00:00:00
abstract：:In recent years, significant effort has been made to identify genes that influence breast cancer risk. Because the high-penetrance breast cancer susceptibility genes BRCA1 and 2 play a role only in a small fraction of breast cancer cases, understanding the genetic risk of the majority of breast cancers will require th...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-12-15 00:00:00
abstract：:The effects of the protein kinase C (PKC) activators, phorbol ester 12-O-tetradecanoyl-13-phorbol acetate (TPA) and the marine natural product, bryostatin 1, on the growth and morphology of human breast cancer cell lines were examined. TPA (1 to 100 nM) inhibited growth of four of six cell lines by up to 75% in 5-day ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1992-03-01 00:00:00
abstract：:A novel method for high-efficiency and region- controlled in vivo gene transfer was developed by combining in vivo electroporation and intraarterial plasmid DNA injection. A mammalian expression plasmid for the Escherichia coli lacZ gene (driven with a SV40 early promoter) was injected into the internal carotid artery...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1996-03-01 00:00:00
abstract：:EBV-infected B-cell lymphomas are a potentially life-threatening complication in bone marrow and solid organ transplant recipients. Immunosuppressive drugs required to prevent allograft rejection also impair anti-EBV T-cell immunity, thereby increasing the risk of EBV-associated disease. Here we demonstrate that the i...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2003-08-01 00:00:00
abstract：:Sequential morphological changes occurring after brief carcinogen exposures of heterotopic tracheal transplants in rats were semiquantitatively studied. Tracheas were exposed to 7,12-dimethylbenz(a)anthracene for 1, 2, or 4 weeks, during which time means of 138, 152, and 160 microgram 7,12-dimethylbenz(a)anthracene, r...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1979-12-01 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：: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：:Noncytotoxic spleen cells from BALB/c mice bearing 15- to 26-mm (but not 29-mm) s.c. MOPC-315 tumors that were cultured in medium containing 2% polyethylene glycol 6000 (PEG) developed substantial levels of anti-MOPC-315 cytotoxicity as assayed by 51Cr release. The level of cytotoxicity obtained increased with progres...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1980-12-01 00:00:00
abstract：:Capan 1, a human pancreatic cancer cell line, is routinely grown in 10% fetal calf serum (FCS). In order to characterize the factors needed for its proliferation, FCS was replaced by a synthetic serum (Ultroser G). For Capan 1 proliferation we found that Ultroser G was as efficient as FCS. A subfraction of Ultroser G ...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-07-15 00:00:00
abstract：:The modifying effect of four dose levels of butylated hydroxytoluene (BHT) on liver and bladder carcinogenesis by N-2-fluorenylacetamide (FAA) was studied in rats. FAA (200 ppm) was fed simultaneously with four levels of BHT (300, 1000, 3000, and 6000 ppm) to male F344 Fischer strain rats. Groups of animals were kille...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1984-04-01 00:00:00
abstract：:Solid tumor metastasis often involves detachment of epithelial carcinoma cells into the vasculature or lymphatics. However, most studies of cytoskeletal rearrangement in solid tumors focus on attached cells. In this study, we report for the first time that human breast tumor cells produce unique tubulin-based protrusi...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-07-6589
更新日期：2008-07-15 00:00:00
abstract：:2'-Deoxycoformycin (2'-dCF), a tight-binding inhibitor of adenosine deaminase, was administered to 26 pediatric patients with acute lymphoblastic leukemia in a Phase I study. Doses ranged from 0.25 to 1.0 mg/kg given i.v. for 3 consecutive days. Common toxicity included nausea, vomiting, diarrhea, hepatocellular enzym...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1981-09-01 00:00:00
abstract：:The production of CD73-derived adenosine (Ado) by Tregs has been proposed as a resistance mechanism to anti-PD-1 therapy in murine tumor models. We reported that human Tregs express the ectonucleotidase CD39, which generates AMP from ATP, but do not express the AMPase CD73. In contrast, CD73 defined a subset of effect...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-17-2405
更新日期：2018-07-01 00:00:00
abstract：:Heregulin (HRG) is a member of the neuregulin family of ligands that have been shown to interact with and activate erbB receptors. A transgenic mouse model in which full-length HRG is overexpressed has proven that this protein can induce carcinomas in the murine mammary gland. These tumors display a high level of apop...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：2000-07-15 00:00:00
abstract：:Hepatocellular carcinoma is the fifth most common cancer worldwide, and there is no effective therapy for unresectable disease. We have developed a targeted systemic therapy for hepatocellular carcinoma. The gene for a foreign enzyme is selectively expressed in the tumor cells and a nontoxic prodrug is then given, whi...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-05-0393
更新日期：2005-06-15 00:00:00
abstract：:Lymphocytes can be stimulated to proliferate in vitro by mitogens such as concanavalin A. The tumor-promoting phorbol ester 12-O-tetradecanoyl phorbol-13-acetate (TPA) can enhance this proliferation, partly because of an increase in interleukin 2 (IL-2) production. However, if lymphocytes are treated with TPA for 24 h...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1991-01-01 00:00:00
abstract：:Inhibition of PACE4, a proprotein convertase that is overexpressed in prostate cancer, has been shown to block cancer progression in an androgen-independent manner. However, the basis for its overexpression and its growth-inhibitory effects are mitigated and uncertain. Here, we report that PACE4 pre-mRNA undergoes DNA...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.CAN-17-1397
更新日期：2017-12-15 00:00:00
abstract：:Knockout and expression studies suggest that estrogen receptor beta (ERbeta) plays a prominent role in ovarian function and pathology. Moreover, ovarian cancers are characterized by high morbidity and low responsiveness to anti-estrogens. Here we demonstrate, using quantitative PCR to measure ERalpha and ERbeta levels...
journal_title：Cancer research
pub_type： 杂志文章,收录出版
doi：10.1158/0008-5472.CAN-04-0552
更新日期：2004-08-15 00:00:00
abstract：:Glucocorticoids are widely used for the treatment of multiple myeloma. To investigate the direct actions of glucocorticoids on myeloma cells, we have used three cell lines of human multiple myeloma, OPM-1, OPM-2, and RPMI 8226. When growth curves of these cells were examined, OPM-1 cells were resistant, while OPM-2 we...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1990-03-15 00:00:00
abstract：:10-Ethyl-10-deazaaminopterin (10-EDAM) is an analogue of methotrexate with improved preclinical anticancer activity, more selective entry, and greater conversion to polyglutamate forms in neoplastic cells. In this Phase I trial, we have treated 62 adults with advanced solid tumors, giving 10-EDAM i.v. on either a week...
journal_title：Cancer research
pub_type： 临床试验,杂志文章
doi：
更新日期：1988-10-01 00:00:00
abstract：:Anguidine, a protein synthesis inhibitor, has been shown to induce a reversible cell cycle arrest in exponentially growing Chinese hamster ovary cells. The effect of pretreatment with anguidine on the cytotoxicity of subsequently administered various chemotherapeutic agents, hyperthermia, and radiation was investigate...
journal_title：Cancer research
pub_type： 杂志文章
doi：
更新日期：1983-07-01 00:00:00
abstract：:Detecting the presence and diversity of low-level mutations in human tumors undergoing genomic instability is desirable due to their potential prognostic value and their putative influence on the ability of tumors to resist drug treatment and/or metastasize. However, direct measurement of these genetic alterations in ...
journal_title：Cancer research
pub_type： 杂志文章
doi：10.1158/0008-5472.can-03-3652
更新日期：2004-04-01 00:00:00
