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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A case of T lymphoblastic leukemia (T-ALL) showing t(1;7)(p34;q34) as the sole karyotypic abnormality was investigated at the molecular level. Screening of a phage library of tumor DNA with a probe for the beta T cell receptor gene (TCRB), which maps to chromosomal band 7q34, resulted in the isolation of a clone containing DNA spanning the translocation breakpoint of the der(1) chromosome. This clone contained chromosome 1 DNA juxtaposed upstream of a D beta-J beta joint. Cloning of the corresponding germline region of chromosome 1 resulted in the isolation of a phage containing the breakpoint from the reciprocal, der(7), product, which showed chromosome 1 DNA joined downstream to a V beta segment. Comparison of germline and translocation clones demonstrated that breakage of chromosome 1 had occurred at the border of a tandem repeat of Alu sequences. To search for transcripts from DNA near the breakpoint, a chromosomal walk was initiated along chromosome 1. A probe consisting of chromosome 1 DNA from 24-30 kb upstream of the breakpoint hybridized to a transcript derived from the gene encoding the lymphocyte-specific tyrosine kinase p56lck, previously mapped to chromosomal band 1p34. The nonrandom nature of the breakpoints in this case was confirmed by the analysis of a second independent case of T-ALL containing a t(1;7) translocation, which was also found to show breakage within the LCK locus. The chromosomal breakpoint in the first case was localized 2 kb upstream of the lck upstream promoter and first nontranslated exon, while the breakpoint of the second case lay between the two alternative lck promoters, upstream of the second exon. Relative to normal thymus and activated T cells, levels of lck mRNA were greatly elevated in the first case and moderately elevated in the second. The existence of these translocations raises the possibility that alterations in the promoter region of the LCK locus may play a role in human cancer.
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PMID:Chromosomal translocations joining LCK and TCRB loci in human T cell leukemia. 168 Sep 58

A procedure has been developed for the isolation of a catalytically competent phosphorylated tyrosine kinase (RSV Y-kinase) from avian sarcoma virus-induced rat tumors. The procedure involves reaction of partially purified RSV Y-kinase with ATP to effect tyrosyl phosphorylation of catalytically competent RSV Y-kinase. Tyrosyl phosphorylated RSV Y-kinase was isolated from the heterogeneous reaction mixture by immunoadsorption on immobilized phosphotyrosyl binding antibodies and elution with the hapten p-nitrophenyl phosphate. Estimation of the phosphate content of the purified phosphorylated RSV Y-kinase indicated that 1-3 tyrosyl groups had been phosphorylated upon reaction with ATP. The specific activity toward histone 2B of the purified phosphorylated RSV Y-kinase was at least 30-fold greater than that estimated for the RSV Y-kinase prepared previously by immunoadsorption on immobilized antiserum from tumor bearing rabbits.
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PMID:Isolation of a catalytically competent phosphorylated tyrosine kinase from Rous sarcoma virus-induced rat tumor by immunoadsorption to and hapten elution from phosphotyrosine binding antibodies. 169 27

The neu receptor oncoprotein tyrosine kinase, capable of transforming cultured fibroblasts and causing mammary carcinomas in transgenic mice, carries a point mutation in its transmembrane domain and shows a constitutive tyrosine kinase activity. We analyzed the neu tyrosine kinase and its substrates in transfected NIH 3T3 fibroblasts by phosphotyrosine immunoblotting. Tyrosine phosphorylated proteins were similar but not identical in epidermal growth factor (EGF)-stimulated cells expressing the human EGF receptor (EGFR) or a chimeric EGFR/neu receptor but differed from phosphotyrosyl proteins constitutively expressed in neu oncogene-transformed cells. The neu oncoprotein in the latter cells was phosphorylated in tyrosine in a ligand-independent manner and had a shortened half-life in comparison with the normal neu protein. Tumor promoter pretreatment inhibited ligand-induced receptor tyrosine phosphorylation and decreased tyrosine phosphorylated neu oncoprotein. Prolonged pretreatment with 12-O-tetradecanoyl-phorbol-13-acetate (TPA) also prevented the induction of immediate early growth factor-regulated genes in response to neu activation. Expression of the neu oncogene but not the protooncogene in NIH 3T3 cells was associated with enhanced levels of the jun and fos oncoproteins and loss of serum growth factor induction of immediate early mRNA responses. The constitutively activated neu oncoprotein tyrosine kinase thus deregulates cellular genomic responses to growth factors.
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PMID:Constitutively activated neu oncoprotein tyrosine kinase interferes with growth factor-induced signals for gene activation. 170 46

Epidemiological and animal studies suggest a role for calcium in the chemoprevention of colorectal neoplasia. This study was designed to investigate whether supplemental oral calcium has a suppressant effect on colonic mucosal ornithine decarboxylase (ODC) and tyrosine kinase activities in patients with adenomatous polyps or a history of adenomatous polyps and whether this is affected by age. ODC and tyrosine kinase activities were measured in rectal mucosal biopsies of 19 male patients (age, years 46-85 years; mean, 66 years) with adenomatous polyps or a history of adenomatous polyps before and after 1 week of calcium supplementation p.o. (CaCO3; 2500 mg/day) and 2 weeks after cessation of calcium treatment. The basal rectal mucosal ODC activity of patients greater than or equal to 64 years old was nearly 4-fold higher than that of patients less than 64 years old (P less than 0.005). In patients greater than or equal to 64 years old, there was a significant decrease in rectal mucosal ODC activity following 1 week of calcium p.o. compared to those age less than 64 years (P less than 0.05). Overall tyrosine kinase activity did not differ significantly in either patient group before or after calcium supplementation p.o. However, the concentration of phosphotyrosine membrane proteins with molecular weights between 40,000 and 60,000 and between 80,000 and 100,000 were suppressed in patients age greater than or equal to 64 years after 1 week of calcium treatment p.o. These patients also had a corresponding decrease in their rectal mucosal ODC activity. Alternatively, patients whose ODC was not affected by calcium showed no apparent change in the relative concentration of rectal mucosal phosphotyrosine membrane proteins. Our data indicate that there is an age-related increase in basal rectal mucosal ODC activity in patients with adenomatous polyps which can be suppressed with calcium supplementation p.o., suggesting a role for dietary calcium in the chemoprevention of colorectal neoplasia.
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PMID:Supplemental calcium suppresses colonic mucosal ornithine decarboxylase activity in elderly patients with adenomatous polyps. 171 10

The ros1 gene was detected originally by virtue of its transforming potential; the cDNA of the human protooncogene was isolated from a tumor cell line expressing the gene ectopically. It encodes a receptor-type tyrosine specific protein kinase which is closely related to sevenless in Drosophila. Here we report the novel and remarkable in vivo expression pattern of c-ros1, which was determined in the mouse. By a combination of RNase protection and in situ hybridization, we find transient c-ros1 expression during development in the kidney, intestine and lung, coinciding with major morphogenetic and differentiation events in these organs. This temporally restricted nature of expression is unusual for tyrosine kinase receptors and suggests a role for ros1 during development. Furthermore, in kidney development c-ros1 transcripts are confined to subgroups of ureter cells known to be involved directly in inductive interactions between ureter epithelium and metanephric mesenchyme. Thus, this study implicates for the first time a tyrosine kinase receptor in mesenchymal epithelial interactions and suggests a molecular basis for these important inductive events in development.
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PMID:Transient and locally restricted expression of the ros1 protooncogene during mouse development. 171 42

An increasing number of polypeptide growth factors have been identified that regulate not only cell proliferation but also an extraordinary range of cell activities, including matrix protein deposition and resolution, the maintenance of cell viability, cell differentiation, inflammation, and tissue repair. Normal cells appear to require growth factors for proliferation and for maintenance of viability. Cells that secrete a polypeptide growth factor have an advantage in growth. These factors can act either externally through cell surface receptors or internally during the transport of receptors and growth factors through the endoplasmic reticulum and Golgi apparatus, causing autocrine stimulation of cell growth. Depending on the cell type, growth factors can also be potent inhibitors of cell growth rather than stimulators of growth, and the effect can depend on the presence or absence of growth factors. Among the growth factors considered, IGFs are unusual in that they function both as endocrine and as autocrine/paracrine agents. IGF-II, which is associated with fetal growth, is the IGF most frequently expressed by tumors. There is now convincing evidence that some tumors secrete sufficient IGF-II to have systemic endocrine effects as recognized as nonislet cell tumor hypoglycemia. PDGF is normally highly concentrated in platelets and has major significance in stimulation of cellular proliferation in inflammation and wound repair. Normally, this proliferation is self-limited, but the secretion of PDGF by tumors and its effects on cell proliferation of tumors persist. The fact that PDGF B monomer has an identical structure with that of the proto-oncogene C-cis further strengthens the connection between PDGF and tumor growth. EGF has a restricted role in normal physiology, but its close relative, TGF-alpha, is widely distributed in normal and neoplastic tissues. The common receptor for EGF and TGF-alpha is present in many normal and neoplastic cell types. The EGF receptor is the product of the C-erb gene. The oncogene V-cis is a truncated form of the EGF receptor whose tyrosine kinase activity is not dependent on ligand binding. TGF-beta exists in multiple forms. Although it can transform the morphology of certain cell lines in culture, it probably does not act generally as a mitogenic agent. Its major physiologic role in the body appears to be the stimulation of mesenchymal matrix formation. It is of special importance in the regulation of bone matrix formation. Its expression is increased in many tumors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Tumor secretion of growth factors. 171 47

The effect of herbimycin A, an ansamycin antibiotic which inhibits cellular transformation by retroviral tyrosine kinases, on the monolayer growth of seven colon tumor cell lines and one cell line established from normal colonic mucosa, CCL239, was examined. Each colon tumor cell line tested showed dose-dependent growth inhibition in response to herbimycin A. A 125ng ml-1 dose of the antibiotic caused greater than 40% growth inhibition in all colon tumor cell lines after two cell doublings. In contrast, at similar herbimycin A concentrations only 12% inhibition was observed in 'normal' CCL239 cells. No major morphologic changes were observed at the light microscopic level in any of the tumor cell lines or CCL239 cells in response to treatment with herbimycin A. Studies using the HT29 colon adenocarcinoma cell line showed dose-dependent inactivation of pp60c-src by herbimycin A, resulting in decreased autophosphorylation, enolase phosphorylation and steady-state levels, which correlated with cellular growth inhibition. Herbimycin A-induced reductions in pp60c-src kinase activity preceded changes in pp60c-src steady-state levels. Growth and pp60c-src inhibition were reversible following removal of herbimycin A from cell culture media. Our results suggest that regulation of pp60c-src tyrosine kinase activity may be important in growth control of colon tumor cells.
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PMID:Effect of herbimycin A on growth and pp60c-src activity in human colon tumor cell lines. 171 64

The in vitro proliferation of the spontaneous lymphoid T-cell leukemia designated LB was enhanced by physiological, intermediate and supraphysiological concentrations of insulin. The enhancing effect was observed in both serum-free medium (SFM) and medium containing low concentrations of serum. Guinea-pig anti-insulin serum, but not guinea-pig normal serum, inhibited the proliferation of LB cells incubated either in medium containing serum alone or in medium containing serum and supplemented with insulin. This finding suggests that LB cells use serum insulin as a growth factor. Insulin-like growth factors I (IGF-I) and II (IGF-II) failed to stimulate an appreciable proliferation in LB cells, whereas in the same experiment insulin markedly enhanced the proliferation of this lymphoid leukemia. Furthermore, the concentration of unlabelled insulin required to displace 50% of 125I-insulin bound to LB cells was 3 orders of magnitude lower than the concentration of IGF-I required to achieve the same displacement. Our findings indicate that interaction of insulin with its own receptor, and not with IGF-I receptor, triggers the proliferation of LB cells. Radio-receptor assays revealed that LB cells express approximately 3,200 molecules of high affinity (Kd = 10(-9) M) insulin receptor per cell. None of 7 other tumor cell lines tested responded to insulin. The proliferation of insulin-stimulated LB cells was also inhibited with tyrphostin, a tyrosine kinase blocker analogous to tyrosine, which perhaps blocks the tyrosine kinase activity of the insulin receptor beta-chain.
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PMID:Insulin dependence of murine lymphoid T-cell leukemia. 172 17

In this report we describe the identification and characterization of a novel tumor-associated receptor-type tyrosine kinase (hek). We produced a monoclonal antibody (III.A4) that detected a novel glycoprotein on the immunizing pre-B cell acute lymphoblastic leukemia cell line (LK63). This antigen was shown to be expressed sporadically on hemopoietic tumor cell lines and on ex vivo tumors. However, using antibody staining, the molecule was undetectable on normal tissues. Further biochemical characterization showed this molecule (hek) to be a phosphoroprotein. This observation taken together with the tumor-associated nature of hek expression suggested that hek might be a receptor-type protein tyrosine kinase. This was demonstrated by affinity purification of hek. In in vitro kinase experiments the purified hek protein was autophosphorylated on tyrosine and also mediated tyrosine phosphorylation of casein. Purified hek was subjected to N-terminal amino acid sequence analysis which showed that hek had a unique N terminus. Amino acid sequence determination of peptides from a V8 protease digest of hek yielded one 21-amino acid stretch of sequence which showed close homology with the eph subfamily of protein tyrosine kinases. These studies show hek to be a novel human tumor-associated protein tyrosine kinase, which by analogy with previously characterized protein tyrosine kinase proto-oncogenes, may have a role in tumorigenesis.
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PMID:Isolation and characterization of a novel receptor-type protein tyrosine kinase (hek) from a human pre-B cell line. 173 82

The epidermal growth factor receptor (EGFR) and the protein products of c-erbB-2 and c-met proto-oncogenes belong to a family of growth factor receptors with tyrosine kinase activity. In human colonic carcinomas, the expression of the EGFR and c-erbB-2 have been studied at the protein level only, while c-met expression has not been reported. We have examined the mRNA expression of these genes in human normal colorectal mucosa and primary carcinomas. The results demonstrate that the normal mucosa shows highly variable levels of EGFR and c-erbB-2 mRNAs, but expresses consistently low amounts of c-met mRNA. Colorectal carcinomas did not express significantly higher levels of the EGFR and c-erbB-2 mRNAs than the normal mucosa. In contrast, c-met was consistently and significantly overexpressed (mean sixfold) in carcinomas as compared with normal mucosa. Seventy percent of paired normal-tumor specimens showed a tumor to normal c-met mRNA ratio of greater than 4. The expression of c-met mRNA was also enhanced in the adenomas, suggesting that over-expression of this proto-oncogene may have mechanistic significance in the early stages of human colorectal carcinogenesis.
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PMID:Overexpression of c-met proto-oncogene but not epidermal growth factor receptor or c-erbB-2 in primary human colorectal carcinomas. 174 Nov 62


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