Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:2.7.10.1 (ERK)
95,504 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Published reports indicate that normal rodent cells can grow in medium containing either L-methionine or L-homocysteine, whereas malignant rodent cells have an absolute requirement for L-methionine. Our studies with two normal human cell lines (fetal lung fibroblasts and bladder epithelial cells) exhibit equal growth in media containing either L-methionine or L-homocysteine. The same is true for five malignant human cell lines (carcinoma of the cervix [HeLa], adenocarcinoma of the breast [AlAb], acute lymphoblastic leukemia [MOLT-3], Wilms' tumor [SK-NEP-1], and reticulum cell sarcoma [T-77], whereas four other malignant cell lines (adenocarcinoma of the breast [SK-BR-2-III], the two lymphoblastic leukemias [CCRF-HSB-2 and CCRF-SB], and a neuroblastoma [SK-N-MC]) have absolute requirements for L-methionine. Two malignant cell lines, an adenocarcinoma of the lung (A549) and an adenocarcinoma of the pancreas (Capan-1), showed restricted growth under the experimental conditions used. L-Methionlinase (L-methionine-alpha-deamino-gamma-mercaptomethane-lyase, EC 4.4.1.11) at a concentration of 0.1 unit/ml leads to complete growth inhibition of cell cultures of both the normal human fetal lung fibroblasts (F-136-35-56) and the acute lymphoblastic leukemia (CCRF-HSB-2). L-Homocysteine-thiolactone in medium containing L-methioninase could partly "rescue" the normal but not the malignant cells.
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PMID:Tumor therapy by deprivation of L-methionine: rationale and results. 46 46

The fms-like tyrosine kinase 4 (FLT4) complementary DNA was cloned from a human HEL erythroleukemia cell library by polymerase chain reaction-amplification. We previously reported a partial sequence of FLT4 and showed that the FLT4 gene maps to chromosomal region 5q33-qter (O. Aprelikova, K. Pajusola, J. Partanen, E. Armstrong, R. Alitalo, S. Bailey, J. McMahon, J. Wasmuth, K. Huebner, and K. Alitalo, Cancer Res., 52: 746-748, 1992). Here we present the full-length sequence of the predicted FLT4 protein. The extracellular domain of FLT4 consists of 7 immunoglobulin-like loops, including 12 potential glycosylation sites. On the basis of structural similarities FLT4 and the previously known FLT1 and kinase insert domain-containing receptor tyrosine kinase/fetal liver kinase 1 (KDR/FLK1) receptors constitute a subfamily of class III tyrosine kinases. FLT4 was expressed as 5.8- and 4.5-kilobase mRNAs which were found to differ in their 3' sequences and to be differentially expressed in the HEL and DAMI leukemia cells. Interestingly, a Wilms' tumor cell line, a retinoblastoma cell line, and a nondifferentiated teratocarcinoma cell line expressed FLT4, whereas differentiated teratocarcinoma cells were negative. Most fetal tissues also expressed the FLT4 mRNA, with spleen, brain intermediate zone, and lung showing the highest levels. In in situ hybridization the FLT4 autoradiographic grains decorated bronchial epithelial cells of fetal lung. No evidence was obtained for the expression of FLT4 in the endothelial cells of blood vessels.
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PMID:FLT4 receptor tyrosine kinase contains seven immunoglobulin-like loops and is expressed in multiple human tissues and cell lines. 132 15

Rat nephroblastoma (Wilms' tumor) was induced by transplacental administration of N-ethyl-nitrosourea (ENU). The induced renal tumors were histologically compatible with human nephroblastoma. A cultured cell line (ENU-T-1) established from a xenotransplant, showed similar morphological and biological features to cultured embryonal kidney cells. Introduction of normal human chromosome #11 (#11) bearing Wilms' tumor suppressor gene(s) (WT) suppressed colony-forming ability on soft agar plates (CFA) but tumorigenicity of ENU-T-1 was not affected. Whereas tumorigenicity of human nephroblastoma cell line, SK-NEP-1 was completely suppressed, CFA was unchanged. These facts indicated that pathogenetic mechanism is different between human and experimental rat nephroblastomas.
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PMID:Characterization of experimental rat nephroblastoma and its cell line. 133 5

The rap1/Krev-1 gene encodes a ras-related protein that suppresses transformation by ras oncogenes. We have purified an 88 kd GTPase activating protein (GAP), specific for the rap1/Krev-1 gene product, from bovine brain. Based on partial amino acid sequences obtained from this protein, a 3.3 kb cDNA was isolated from a human brain library. Expression of the cDNA in insect Sf9 cells resulted in high level production of an 85-95 kd rap1GAP that specifically stimulated the GTPase activity of p21rap1. The complete deduced amino acid sequence is not homologous to any known protein sequences, including GAPs specific for p21ras. Northern and Western blotting analysis indicate that rap1GAP is not ubiquitously expressed and appears most abundant in fetal tissues and certain tumor cell lines, particularly the Wilms' kidney tumor, SK-NEP-1, and the melanoma, SK-MEL-3, cell lines.
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PMID:Molecular cloning of a GTPase activating protein specific for the Krev-1 protein p21rap1. 190 17

The ability of normal human fibroblast-derived chromosomes to suppress tumorigenicity in nude mice and in vitro growth properties of various tumor cell lines was examined. Normal human chromosomes tagged with pSV2neo gene by DNA transfection were transferred to the following human tumor cell lines by microcell-fusion: SiHa (uterine cervical carcinoma), A204 (rhabdomyosarcoma), SK-NEP-1 (Wilms' tumor), HHUA (uterine endometrial carcinoma), SK-N-MC (neuroblastoma), YCR (renal cell carcinoma), HT1080 (fibrosarcoma), and CC1 (chorionic carcinoma). The results indicate the presence of a putative tumor-suppressor gene(s) in multiple chromosomes, and suggest that multiple genes may normally be involved in suppressing the transformed phenotypes at different stages in some tumors. Thus, the microcell transfer of chromosomes to specific tumor cell lines is a useful technique to demonstrate the presence of tumor-suppressor genes on individual chromosomes, and may also be useful in cloning of tumor-suppressor genes as well as elucidating their function in cell-growth and differentiation.
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PMID:Multiple chromosomes carrying tumor suppressor activity, via microcell-mediated chromosome transfer, for various tumor cell lines. 248 35

The presence of neonatal (cord) lymphokine-activated killer (LAK) cell activity toward natural killer cell resistant Raji and Daudi cell lines has recently been reported from our laboratory. We investigated the future therapeutic use of LAK adoptive immunotherapy by examining LAK in vitro cytotoxicity from both neonatal and adult mononuclear cells against solid tumor cell lines of relevance to pediatric oncology: SH-SY5Y (neuroblastoma), SK-NM-C (neuroblastoma-neuroepithelioma), NEP-1 (Wilms' tumor), SK-ES-1 (Ewing's sarcoma), and A-204 (rhabdomyosarcoma). Cord and adult mononuclear cells were activated by recombinant IL-2 (100 mu/ml) for 5-7 days and added in an effector:target ratio of 40:1 to 51Cr-labeled target cells. Specific cell lysis was determined after a 4-h incubation. There was a significantly high level of cord and adult LAK cytotoxicity against Wilms' (76.4 +/- 9.8 versus 77.3 +/- 6.8%) and Ewing's (84.2 +/- 5.5 versus 71.1 +/- 6.5%) cell lines and significant but moderate LAK activity against neuroepithelioma (52.0 +/- 6.6 versus 55.4 +/- 4.5%) and rhabdomyosarcoma (46.6 +/- 5.7 versus 43.9 +/- 5.2%) cell lines. There was no difference between cord and adult LAK activity toward these targets. However, a differential response toward the more classical neuroblastoma cell line, SH-SY5Y, was noted with significantly more LAK cytotoxicity from cord mononuclear cells than adult mononuclear cells (51.2 +/- 6.9 versus 28.5 +/- 8.2%) (p less than or equal to 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Lymphokine-activated killer cytotoxicity in neonatal mononuclear cells: in vitro responses to tumor cell lines from pediatric solid tumors. 253 88

The tumorigenic potential of allogeneic rat kidney cell-lines transformed in vivo by a carcinogenic dose of dimethylnitrosamine (DMN) was investigated by intravenous injection of single cell suspensions into neonatal outbred rats within 24 h of birth. The cell-lines tested included mesenchymal populations obtained from DMN-induced renal mesenchymal tumors (RRMT-2,-8,-9) and transformed mesenchymal (TRKM-5,-7,-8) and epithelial (TRKE-1) cell-lines derived from the kidneys of rats treated only hours previously with the carcinogen. Additionally, spontaneous nephroblastoma-derived embryonal cell-lines (REN-1,-2) were included in the study to extend the potential of the neonatal rat system over a range of differentiation lineages. The transplantation system proved to be a rapid and efficacious assay for demonstrating the malignancy of the mesenchymal and embryonal cell-lines. The major sites for tumor growth were the lungs, heart and eye, but differences in organ predilection were observed for individual cell-lines. The transformed epithelial cell-line (TRKE-1) proved refractory to the single intravenous inoculation but was transplantation-positive when a follow-up subcutaneous dose was administered several days later. The resultant growths produced by the diverse differentiation lineages were histologically characteristic for the tumor tissue affiliate of each cell-line. The results demonstrate the utility of this transplantation system for testing the malignant potential of morphologically transformed cells across the allogeneic barrier as well as proving that DMN is capable of inducing malignant transformation in both mesenchymal and epithelial cell types of the rat kidney after a very short period of exposure in vivo.
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PMID:Demonstration of the tumorigenicity of transformed rat kidney cell-lines by intravenous allotransplantation in the neonate. 712 74

Wilms tumor is a pediatric neoplasm that arises from the metanephric blastema. The expression of the gene encoding insulin-like growth factor II (IGF-II) is often elevated in these tumors. Since many of the actions of IGF-II are mediated through activation of the IGF-I receptor (IGF-IR), we have measured the levels of IGF-IR mRNA in normal kidney and in Wilms tumor samples using solution hybridization/RNase protection assays. IGF-IR mRNA levels in the tumors were 5.8-fold higher than in adjacent normal kidney tissue. Among the tumors themselves, the levels of IGF-IR mRNA in those containing heterologous stromal elements were 2-fold higher (P < 0.01) than in tumors without these elements. IGF-IR gene (designated IGF1R) expression in the tumors was inversely correlated with the expression of the Wilms tumor suppressor gene WT1, whose inactivation appears to be a key step in the etiology of Wilms tumor. Cotransfection of Chinese hamster ovary cells with rat and human IGF-IR gene promoter constructs driving luciferase reporter genes and with WT1 expression vectors showed that the active WT1 gene product represses IGF-IR promoter activity in a dose-dependent manner. These results suggest that underexpression, deletion, or mutation of WT1 may result in increased expression of the IGF-IR, whose activation by IGF-II may be an important aspect of the biology of Wilms tumor.
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PMID:Increased expression of the insulin-like growth factor I receptor gene, IGF1R, in Wilms tumor is correlated with modulation of IGF1R promoter activity by the WT1 Wilms tumor gene product. 839 Jun 84

Relapsed Wilms tumor is often very responsive to re-treatment, and cures are possible in many cases. Recurrent Wilms tumor forms a heterogeneous group because initial therapies vary widely. Given the complexity of the problem, there is a great need for an organized clinical investigative approach. Ideally, the treatment of initial relapse should be specified by the primary treatment protocol in order to better evaluate overall survival as an end-point for new primary therapy strategies. This is especially appropriate for Wilms tumor, because the investigations of this tumor over the last 20 years have attempted to determine the minimal therapy necessary for cure. Thus, survival rather than relapse-free survival is the most appropriate criterion for the success of a primary retreatment regimen. This investigative approach would also allow evaluation of treatment strategies tailored to a specific patient population. Important questions remain for those who treat recurrent Wilms tumor. Defining the role of high-dose therapy, defining the role of total body irradiation in high-dose therapy regimens, and defining the benefit and toxicity of cyclophosphamide compared with ifosfamide are three current questions under investigation. Developing new agents and regimens effective against Wilms tumor, especially against anaplastic tumors, RTK, and CCSK, is extremely important if progress is to be made in treating these tumors after relapse. Finally, there is a strong need to develop biologic information about tumors that recur, so not only will we better understand why patients relapse but also we can develop therapy tailored specifically to the biology of the recurrent tumor.
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PMID:The management of relapsed Wilms tumor. 859 66

In patients with Denys-Drash syndrome, mutations of the Wilms' tumor suppressor gene are associated with nephroblastomas and developmental abnormalities of the genital tract and renal glomerulus. Normally, the Wilms' tumor gene product (WT1) is expressed at high levels in visceral glomerular epithelial cells (VGEC) of the emerging fetal glomerulus. We demonstrate that WT1 could normally serve to suppress EGF receptor expression in VGEC, since immunoreactive EGF receptor is strikingly absent compared to epithelial cells of the emerging proximal and distal tubule, which lack WT1. When HEK293 cells were co-transfected with plasmids containing EGFR enhancer/promoter elements linked to a CAT reporter and plasmids containing WT1 cDNA, EGFR enhancer/promoter activity was suppressed by all wild-type WT1 isoforms, but not by deletion mutants of WT1 lacking normal zinc-finger or N-terminal domains. Surprisingly, plasmids expressing a Denys-Drash WT1 mutant (R394W) retained the ability to suppress EGFR promoter activity in this system. Furthermore, we found that immunoreactive EGFR was appropriately undetectable in glomeruli from a three-year-old girl with Denys-Drash syndrome and in sections of her Wilm's tumor. These data suggest that faulty suppression of EGFR cannot account for the abnormalities of glomerulogenesis seen in Denys-Drash patients.
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PMID:Regulation of renal EGF receptor expression is normal in Denys-Drash syndrome. 929 Nov 79


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