Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Incorporation of phosphorus from [gamma-32P]ATP into protein was catalyzed by specific immunoprecipitates from avian sarcoma virus (ASV)-transformed avian and mammalian cells. This incorporation was observed only when antiserum from tumor-bearing rabbits able to specifically precipitate the ASV sarcoma gene product, p60src, was used to immunoprecipitate antigens from transformed cell lysates. Immunoprecipitates of extracts from normal cells or cells infected with a transformation-defective ASV mutant showed no activity in this assay, nor did any immune complexes formed with normal rabbit serum and any of the cell extracts tested. The expression of the protein kinase activity (ATP:protein phosphotransferase, EC 2.7.1.37) was growth temperature-dependent in cells infected with an ASV mutant temperature-sensitive for the transformation. These results on an enzymatic activity associated with the ASV transforming protein are discussed in terms of protein phosphorylation as a mechanism for viral transformation.
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PMID:Protein kinase activity associated with the avian sarcoma virus src gene product. 20 79

Incubation of simian virus 40 (SV40) tumor (T) antigen-containing immunoprecipitates with [gamma-32P]ATP results in the incorporation of radioactive phosphate into large T antigen. Highly purified preparations of large T antigen from a SV40-transformed cell line, SV80, are able to catalyze the phosphorylation of a known phosphate acceptor, casein. The kinase activity migrates with large T antigen through multiple purification steps. Sedimentation analysis under non-T-antigen-aggregating conditions reveals that kinase activity and the immunoreactive protein comigrate as a 6S structure. The kinase activity of purified preparations of large T antigen can be specifically adsorbed to solid-phase anti-T IgG, and partially purified T antigen from a SV40 tsA transformation is thermolabile in its ability to phosphorylate casein when compared to comparably purified wild-type T antigen. These observations indicate that the SV40 large T antigen is closely associated with protein kinase (ATP:protein phosphotransferase, EC 2.7.1.37) activity.
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PMID:Protein kinase activity associated with simian virus 40 T antigen. 22 52

Some biological functions of macrophages can be stimulated by muramyl dipeptide (MDP) in vitro. Such stimulation is more efficient when MDP is bound to macromolecule carriers. The macrophage stimulation by MDP bound to glycosylated serum albumin (BSA) or bound to gluconoylated and glycosylated poly-L-lysine (PLK) is investigated. These two types of MDP conjugates are more efficient than free MDP in rendering mouse peritoneal and rat alveolar macrophages cytostatic against various tumor cells. However, the release of mitogenic factor or cytotoxic factor (CF) by activated macrophages varies according to the nature of the carrier (BSA or PLK) and to the nature and content of sugar residues bound to the macromolecule carrier (mannose or 6-phosphomannose). Macrophages activated by MDP bound to glycosylated BSA release mitogenic factor and CF into the medium; anti-recombinant tumor necrosis factor (rTNF) totally inhibits the cytotoxicity of the supernatant. On the contrary, MDP bound to glycosylated PLK induces no secretion of mitogenic factor and a very small amount of CF in the culture medium. The role of CF in the cytostatic activity of activated macrophages is discussed. The released CF is not involved in the cytostatic activity, but TNF-like molecules, expressed at the membrane level, could be implied because anti-rTNF abrogates 40% of the cytostatic activity of the macrophages.
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PMID:Macrophage activation by muramyl dipeptide bound to neoglycoproteins and glycosylated polymers: cytotoxic factor production. 231 59

In Y1 adrenocortical tumor cells, corticotropin (ACTH), cyclic AMP, and 8-bromoadenosine 3',5'-monophosphate (8BrcAMP) stimulated ornithine decarboxylase activity (L-ornithine carboxy-lyase, EC 4.1.1.17) and steroidogenesis. The concentrations required for half-maximal activation of ornithine decarboxylase were 60 pM for ACTH and 1 mM for 8BrcAMP; the concentrations required for half-maximal activation of steroidogenesis were 50 pM for ACTH and 0.2 mM for 8BrcAMP. Ornithine decarboxylase activity increased 1.5 hr after the addition of these agents, reached a maximum between 4 and 6 hr, and then declined. Mutant clones with impaired ACTH-responsive adenylate cyclase systems [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1]did not respond to ACTH with increased ornithine decarboxylase activity, but they responded normally to added cyclic AMP. These results indicate that adenylate cyclase and cyclic AMP are necessary for the stimulation of ornithine decarboxylase activity by ACTH. In a series of Y1(Kin) mutants with altered cyclic AMP-dependent protein kinase activities (ATP:protein phosphotransferase, EC 2.7.1.37), the effects of ACTH on ornithine decarboxylase also were attenuated. These findings suggest that cyclic AMP-dependent protein kinase also plays a necessary role in the stimulation of ornithine decarboxylase activity by ACTH. The effects of ACTH on ornithine decarboxylase in the Kin mutants, however, were quantitatively different from the effects on steroidogenesis and did not closely reflect the degree of defect in cyclic AMP-dependent protein kinase activity. These differences suggest that the pathways of ACTH action leading to stimulation of steroidogenesis and ornithine decarboxylase activity diverge subsequent to activation of the protein kinase.
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PMID:Regulation of ornithine decarboxylase activity by corticotropin in adrenocortical tumor cell clones: roles of cyclic AMP and cyclic AMP-dependent protein kinase. 624 65

We have identified the nucleotide sequence of the cDNA encoding the human counterpart of the mouse gene Plk (polo-like kinase). The sequence of the human gene, PLK, predicts a serine/threonine kinase of 603 aa. Expression of PLK mRNA appeared to be strongly correlated with the mitotic activity of cells. Resting peripheral lymphocytes did not express the gene at all. When primary T cells were activated by phytohemagglutinin, a high level of PLK transcripts resulted within 2-3 days. In some cases, addition of interleukin 2 to these cells increased the expression of PLK mRNA further. In contrast, primary cultures of human peripheral macrophages, which were not dividing under the culture conditions applied, showed very little or no PLK mRNA. Stimulation of these cells by bacterial lipopolysaccharide, an inducer of several cytokines in macrophages, totally abrogated the expression of PLK mRNA. In line with a function of PLK mRNA expression in mitotically active cells is our finding that six immortalized cell lines examined expressed the gene. In A-431 epidermoid carcinoma cells this expression was down-regulated by serum starvation and enhanced after serum was added again. Tumors of various origin (lung, colon, stomach, smooth muscle, and esophagus as well as non-Hodgkin lymphomas) expressed high levels of PLK transcripts in about 80% of the samples studied, whereas PLK mRNA was absent in surrounding tissue, except for colon. The only normal tissues where PLK mRNA expression was observed were colon and placenta, both known to be mitotically active. No PLK transcripts were found in normal adult lung, brain, heart, liver, kidney, skeletal muscle, and pancreas. In Northern blot experiments with RNA from lymphocytes which were treated with phytohemagglutinin and cycloheximide, PLK transcripts were not detectable, suggesting that PLK is not an early growth-response gene.
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PMID:Induction and down-regulation of PLK, a human serine/threonine kinase expressed in proliferating cells and tumors. 812 74

We have cloned and characterized a putative protein serine/threonine kinase termed prk through a combination of polymerase chain reaction and conventional cDNA library screening approaches. There are apparently two distinct domains within prk protein deduced from its nucleotide sequences. The amino-terminal portion has the feature of the catalytic domain of a serine/threonine kinase and shows strong homology to mouse fnk and other polo family kinases including mouse snk, human and murine plk, Drosophila polo, and yeast Cdc5. The carboxyl-terminal portion, presumably the regulatory domain, shares extensive homology to mouse fnk. Northern blotting analyses reveal that prk expression is restricted to a very limited number of tissues with placenta, ovaries, and lung containing detectable amounts of prk mRNA. prk mRNA expression is also detected at a low level in the megakaryocytic cell line Dami, MO7e, and three brain glioma cell lines. In addition, refeeding of serum-deprived MO7e, Dami, and K562 cells of hematopoietic origin and GMOO637D of lung fibroblasts rapidly activates prk mRNA expression with its peak induction around 2 h after serum addition. prk gene activation by the serum requires no new protein synthesis. The recombinant cytokines such as interleukin-3 and thrombopoietin also activate prk mRNA expression in MO7e cells. Furthermore, a survey of RNAs isolated from the tumor and the uninvolved tissues from 18 lung cancer patients reveals that prk mRNA expression is significantly down-regulated in tumor tissues. Southern blotting analysis indicates that the prk gene is present in a single copy in the genome of tumors and normal cells. Taken together, these results suggest that prk expression may be restricted to proliferating cells and involved in the regulation of cell cycle progression. The molecular cloning of prk cDNA will facilitate the study of its biological role as well as its potential role in tumorigenesis.
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PMID:Prk, a cytokine-inducible human protein serine/threonine kinase whose expression appears to be down-regulated in lung carcinomas. 870 27

During mitosis, the vertebrate cell nucleus undergoes profound changes in architecture. At the onset of mitosis, the nuclear envelope breaks down, the nuclear lamina is depolymerized, and interphase chromatin is condensed to chromosomes. Concomitantly, cytoplasmic microtubules are reorganized into a mitotic spindle apparatus, a highly dynamic structure required for the segregation of sister chromatids. Many of the above events are controlled by reversible phosphorylation. Hence, our laboratory is interested in characterizing the kinases involved in promoting progression through mitosis and in identifying their relevant substrates. Prominent among the kinases responsible for regulating entry into mitosis is the Cdc2 kinase, the first member of the cyclin dependent kinase (Cdk) family. Recently, we found that Cdc2 phosphorylates HsEg5, a human kinesin-related motor protein associated with centrosomes and the spindle apparatus. Our results indicate that phosphorylation regulates the association of HsEg5 with the mitotic spindle and that the function of this plus-end directed motor is essential for centrosome separation and bipolar spindle formation. Another kinase implicated in regulating progression through mitosis is Plk1 (polo-like kinase 1), the human homologue of the Drosophila gene product "polo." By antibody microinjection we have found that Plk1 is required for the functional maturation of centrosomes and hence for entry into mitosis. Furthermore, we found that microinjected anti-Plk1 antibodies caused a more severe block to cell cycle progression in diploid fibroblasts than in immortalized tumor cells. This observation hints at the existence of a checkpoint linking Cdc2 activation to the presence of functional centrosomes.
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PMID:Dynamic changes in nuclear architecture during mitosis: on the role of protein phosphorylation in spindle assembly and chromosome segregation. 898 94

PLK (polo-like kinase) belongs to a family of serine/threonine kinases and represents the human counterpart of polo in Drosophila melanogaster and of CDC5 in Saccharomyces cerevisiae. It is strongly involved in spindle formation and chromosome segregation during mitosis. We have shown previously that PLK mRNA expression correlates with the mitotic activity of cells and the prognosis of lung cancer patients. In this report, the level of PLK protein was analyzed using immunohistochemical techniques. PLK protein was found expressed in the nuclei of tumor cells from lung and breast cancer as well as in several tumor cell lines. Furthermore, in peripheral lymphocytes treated with phytohemagglutinin, elevated proliferative activity of the cells correlated with the up-regulation of PLK protein expression. In contrast, in U937 and HL-60 cells after induction of differentiation with phorbol ester, PLK immunostaining disappeared under conditions of terminal differentiation. Most of the PLK protein was found in the nucleus of proliferating cells with diffuse but distinct staining also in the cytoplasm. Taken together, high levels of PLK protein are associated with cellular proliferation. Combined with other proliferative and oncogene markers, PLK may be useful for improved prediction of the clinical prognosis of cancer patients and for early cancer diagnosis. Due to its activity late in the cell cycle, it may be a target for cancer chemotherapy.
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PMID:Polo-like kinase, a novel marker for cellular proliferation. 909 72

Previous data have shown that the mRNA-expression of the serin/threonine-kinase polo-like kinase (PLK) is closely correlated with the survival of patients suffering from a subset of malignant tumors. PLK-mRNA and protein-expression are restricted to cells in the cell cycle. PLK-mRNA-transcripts are highly abundant in proliferating cells; no gene expression is found in G0-phase cells. Here we investigated the mRNA- and protein-expression of PLK- and estrogen-receptor (ER) in human breast-carcinoma by northern-blotting, RT-PCR and immunohistochemistry. The expression of MIB-I was determined on serial sections. Analysis of the immunohistochemical data revealed a close correlation between the ER and PLK-expression (r = 0.677; p = 0.001, n = 30). No relationship between the mRNA-expression of ER and PLK was found. Furthermore, no correlation for the protein expression of PLK and MIB-I exists. The influence of estrogen (ES) is known to have proliferative potential. The expression of ER correlates with the ES-plasma-level. In addition, the hormone cycle of premenopausal women undergoes rapid vacillations with varying effects on the proliferating tumor cells, e.g., growth induction. Our results therefore show that ER-expression is not only of therapeutic value for the clinician, but it may also be a tool for determining the tumor proliferation index more precisely by integrating the hormone-mediated proliferation stimulus.
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PMID:Polo-like kinase: a novel marker of proliferation: correlation with estrogen-receptor expression in human breast cancer. 1118 70

Epidemiological studies suggest that high intake of dietary fat rich in saturated fatty acids increases the colon cancer risk whereas dietary fish oil high in omega-3 fatty acids reduces the colon cancer risk. Previously, we reported that consumption of omega-6 fatty acid rich diets such as corn oil strongly promotes azoxymethane (AOM)-induced colon carcinogenesis in rats as compared to ingestion of a diet with equivalent amount of fat containing fish oil (HFFO) or low-fat diet (LFCO). Expression of PLK3 (Polo-like kinase-3, previously named Prk) is negatively correlated with the development of certain cancers. Ectopic expression of human PLK3 results in cell cycle arrest or induces apoptosis. To understand the role of PLK3 in colon carcinogenesis and to study the effect of types and amount of dietary fat on the expression levels of PLK3 in colon tumors, we analyzed the colon tumors and mucosa of rats administered the diets containing fish oil and corn oil for PLK mRNA expression. Here we report that expression of PLK3 was down-regulated in rat colon tumors. Quantitative polymerase chain reaction demonstrated that PLK3 mRNA levels were significantly lower in carcinogen (azoxymethane)-induced rat colon tumors than their uninvolved normal colonic mucosa. Among the normal mucosa isolated from rats fed on diets with various levels of fat (LFCO, or high fat diet with corn oil, HFCO, or supplemented with fish oil, HFFO), no significant changes in PLK3 mRNA expression was detected. Tumors isolated from rats fed with HFCO diet contained a very low level of PLK3 mRNA expression. Interestingly, tumors from rats fed the HFFO diet did not exhibit as dramatic down-regulation of PLK3 as the tumors of animals fed the HFCO diet. Furthermore, our results also indicate that the ectopic expression of a kinase active PLK3 construct induced apoptosis in HT-29 colon carcinoma cells. These observations suggest for the first time that a decreased activity of PLK3 may play a key role in colon tumor development as well as in HFCO-induced colon tumorigenesis.
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PMID:Down-regulation of PLK3 gene expression by types and amount of dietary fat in rat colon tumors. 1174 51


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