Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C1326912 (tumorigenesis)
 57,481 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A cell surface-located nucleoside triphosphatase activity can be assayed in liver epithelial cultures in situ with the incubation of intact cells in a medium containing [gamma-32P]adenosine triphosphate and correlated with the tumorigenicity of these cells in neonatal Wistar rats. The ectoenzyme activity of normal diploid cell lines is minimal, whereas a considerably high activity has been found in all tumorigenic cell lines tested. The optimum condition for the adenosinetriphosphatase activity is physiological with regard to osmolarity, ionic composition, pH, and substrate concentration in the medium. The enzyme is significantly stimulated by Ca2+, and its activation is controlled by Mg2+. Histochemical examinations indicate that glutaraldehyde-fixed cells of tumorigenic lines have Ca2+-stimulated adenosinetriphosphatase activity on the external surface. The isotopic assay of adenosine triphosphate hydrolysis by intact cells may provide a rapid method for screening oncogenesis in vitro of liver epithelial cells.
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PMID:Surface membrane nucleoside triphosphatase activity and tumorigenicity of cultured liver epithelial cells. 13 72

Primary cultures of human umbilical vein endothelial cells (HEC) developed extensive cytopathic changes and necrosis after high multiplicity infection with wild-type SV40 virus. Using the calcium co-precipitation technique, stable transformation was obtained with purified preparations of intact circular SV40 DNA and restriction endonuclease-derived linear DNA fragments containing the entire early gene region. Smooth muscle cells, isolated from the same blood vessels, showed neither cytopathic effects nor transformation after similar treatment with SV40 virus or DNA. The HEC cultures transformed by SV40 (SVHEC) expressed SV40-specific T (tumor) and Tr (transplantation) antigens, but not V (viral capsid) antigen. No evidence of infectious virus production was found upon co-cultivation with the CV-1 line of monkey kidney cells. Transformation resulted in markedly increased growth potential, loss of anchorage dependence and topoinhibition of growth, and a reduced serum requirement. Prolonged subcultivation was accompanied by chromosomal abnormalities and eventual "crisis". Transformed cells did not exhibit endothelial-specific organelles (Weibel-Palade bodies) or factor VIII antigen, but angiotensin-converting enzyme occasionally was detectable in SVHEC cultures. SV40-transformed human vascular endothelium, a nonfibroblast diploid cell type, may be useful in studies of oncogenesis and control of the differentiated state.
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PMID:Transformation of cultured human vascular endothelium by SV40 DNA. 18 41

The alpha T3-1 cell line which was derived by targeted tumorigenesis in transgenic mice [Windle et al. (1990) Mol. Endocrinol. 4, 597-603] possesses high-affinity binding sites for GnRH analogs coupled to enhanced phosphoinositide turnover and phospholipase D activity. Incubation of alpha T3-1 cells with [D-Trp6]-GnRH analog (GnRH-A) resulted in a rapid increase in gonadotropin alpha-subunit mRNA levels which was detected already at 30 min of incubation (0.1 nM GnRH-A, 3-fold, p < 0.01). The effect diminished with time to reach basal levels at about 12 h of incubation, with a secondary rise in alpha mRNA levels between 12 and 24 h of incubation. Addition of the protein kinase C activator 12-O-tetradecanoylphorbol 13-acetate (TPA, 100 ng/mL) or the Ca2+ ionophore ionomycin (1 microM) to alpha T3-1 cells also resulted in a rapid increase in alpha-subunit mRNA levels. Surprisingly, GnRH-induced alpha-subunit release was detected only after a lag of 4 h of incubation. Thus, dissociation between exocytosis and gene expression can be demonstrated in GnRH-stimulated alpha T3-1 cell line.
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PMID:Dissociation between release and gene expression of gonadotropin alpha-subunit in gonadotropin-releasing hormone-stimulated alpha T3-1 cell line. 128 29

Various functioning and non-functioning tumors arise from endocrine glands in both the sporadic and familial forms and pathophysiology of the tumors is variable due to differences in the sort of tumor-bearing endocrine organs and in the amount of hormones released. In this paper, gene abnormalities in growth hormone (GH)-secreting pituitary adenoma, ectopic GHRH-producing tumor, multiple endocrine neoplasia (MEN) and ectopic parathyroid hormone (PTH)-producing tumor are documented in relation to etiology and pathophysiology. GH-secreting pituitary adenoma is heterogeneous in clinical features, pathological findings and GH responses to various secretagogues. A point mutation of codon 201 of Gs alpha gene was observed in 2 out of 45 GH-secreting pituitary adenomas (4.4%), but no point mutation of Gi2 alpha gene was found. Pituitary tumors may occur at any stage of differentiation from the totipotent cells to mature anterior pituitary cells, and the mutations of Gs alpha and H-ras genes as well as loss of heterozygosity (LOH) found on chromosome 11 in some adenomas must be involved in their tumorigeneses. Since 1959, 34 patients with ectopic GHRH-producing tumor associated with acromegaly have been reported. In our case of MEN type 1, the paradoxical rise of plasma GH after TRH or glucose administration disappeared after resection of the tumor. The tumor cells showed neither rearrangement nor amplification of GHRH gene and 20 oncogenes including ras, myc, and erb. Only LOHs of HRAS1 and D11S151 were detected in this tumor, but no point mutation was found in HRAS1 gene. Therefore, a kind of tumor suppressor gene may be involved in the tumorigenesis of the tumor in addition to inactivation of MEN-1 locus. In MEN-1 patients, we reported LOH on chromosomes 1, 9, 11 and 16, while we reported point mutation as being present only in Gs alpha gene on chromosome 20. This point mutation was found specifically in GH-secreting pituitary adenoma but not in hyperplastic parathyroid and pancreas adenoma. These data suggest that in MEN-1 patients tumorigenesis occurs and advances from hyperplasia and adenoma to cancer during multistep changes of genes such as inactivation of MEN-1 gene and other tumor suppressor genes and activation of oncogenes. Ectopic PTH-producing tumor was first reported by us in 1989, and this was followed by 2 papers. These patients showed a disturbance of consciousness and high levels of serum calcium and plasma PTH.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:[Pathophysiology and gene abnormalities of endocrine tumors]. 136 16

During two-stage mouse skin tumorigenesis, the mouse c-Ha-ras oncogene undergoes activation by point mutation after initiation with polycyclic aromatic hydrocarbons. Furthermore, initiated epidermal cells containing an activated Ha-ras oncogene have been shown to be resistant to calcium-induced terminal differentiation. However, the relationship between Ha-ras expression and the differentiation process is not well understood in either normal or initiated cells. Before attempting to explore the role of Ha-ras expression in epidermal differentiation during tumorigenesis, we felt that investigation of Ha-ras gene expression in normal primary epidermal cells undergoing differentiation was warranted, since primary cultures of normal newborn and adult keratinocytes presumably contain the stem cells from which skin tumors arise. In the present studies, northern blot analysis was used to compare Ha-ras expression in normal newborn and adult epidermal cells undergoing differentiation. Steady-state levels of Ha-ras mRNA remained unchanged in primary cultures of normal adult epidermal cells during calcium-induced differentiation, whereas steady-state levels of Ha-ras transcripts decreased during calcium-induced differentiation in primary newborn epidermal cells. Differentiation was induced by switching the adult and newborn keratinocytes from medium containing 0.05 mM Ca2+ to medium containing one of three different calcium concentrations (0.15, 0.5, or 1.2 mM Ca2+). The decrease in Ha-ras mRNA levels observed during differentiation in newborn keratinocytes occurred as an intermediate event in the differentiation process, was specific for the Ha-ras gene, and was not due to a general decrease in transcriptional activity during differentiation. Characteristic patterns of keratin 14 gene expression and cornified envelope formation were observed, verifying that the differentiation process had been induced in both the primary adult and newborn epidermal cells. That adult keratinocytes are resistant to the differentiation-induced reduction in Ha-ras mRNA expression observed in newborn keratinocytes may explain the difference in in vivo tumorigenic potentials of newborn and adult skin.
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PMID:Resistance of adult keratinocytes to differentiation-induced decrease in Ha-ras mRNA levels observed in newborn keratinocytes. 150 41

We recently derived a GnRH-responsive pituitary cell line of the gonadotrope lineage (alpha T3-1) by targeted oncogenesis in transgenic mice. Here, we report studies characterizing the GnRH receptors present in these cells and the intracellular responses to GnRH treatment. The receptors in alpha T3-1 cells show specificity for different GnRH analogs, with dissociation constants very similar to those found in normal rat and mouse pituitary. The concentration of receptors is within the range found in normal pituitary. The addition of GnRH or GnRH agonists increases phosphoinositide turnover and protein kinase-C translocation to membranes, and enhances activation of voltage-sensitive calcium channels. However, GnRH does not affect cAMP levels. Analysis of alpha-subunit mRNA levels demonstrated induction by GnRH and phorbol esters. Our results indicate that GnRH initiates a cascade of intracellular events that generate a set of second messengers, one or more of which is involved in the regulation of gene expression. The responses of alpha T3-1 cells to GnRH appear to have characteristics equivalent to those of primary pituitary gonadotropes, indicating the utility of this cell line as a model system for the study of GnRH responses.
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PMID:Intracellular responses to gonadotropin-releasing hormone in a clonal cell line of the gonadotrope lineage. 165 91

A tumour-specific polypeptide designated U90 is one of a set of polypeptides which are encoded by the host cell and are specific for the transformed cell state, being immunoprecipitated by the sera of tumour-bearing animals. The interest in these tumour-specific polypeptides centres on the finding that they are also recognized by antisera raised against herpes simplex virus type 2 (HSV-2)-infected cells, implying some role for HSV-2 in tumorigenesis. The peptide map of HSV-2-induced U90 is indistinguishable from that of U90 present in uninfected tumour cells, including mouse cells transformed by human papillomavirus type 16. In tumour cells, U90 is located principally in the plasma membrane fraction and cannot be induced by heat shock, glucose starvation, or treatment with tunicamycin or calcium ionophore. U90 is not related to either the heat shock protein of Mr 90,000 (HSP90) or the glucose-related polypeptide of Mr 94,000 (GRP94) as determined by peptide mapping and the use of monospecific, monoclonal and antipeptide antibodies. This suggests that U90 is a novel transformation-specific protein which can be induced by infection with HSV-2.
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PMID:A transformation-specific polypeptide distinct from heat shock proteins is induced by herpes simplex virus type 2 infection. 166 99

Carcinogenesis is a complex and multistep process. Numerous inhibitors (either naturally occurring or synthetic) have been identified that can interfere with various phases of carcinogenesis, including the endogenous formation of carcinogens, the activation or detoxification of carcinogens, or events in tumor promotion. Many of these compounds have survived a complex screening program and are currently in or ready for clinical application. In gastrointestinal malignancies, colon neoplasia has been a popular target for chemoprevention. The identification of preneoplastic events in colon mucosa or in the progression of malignancy from adenomas to adenocarcinomas has permitted the study of numerous compounds such as calcium salts, difluoromethylornithine, and prostaglandin synthesis inhibitors on intermediate biomarkers or on the development of recurrent adenomas or cancers. A variety of other compounds with general efficacy in other tumor models have also been shown to be effective inhibitors of tumorigenesis in preclinical models of esophageal, gastric, pancreatic, and hepatic carcinogenesis. This review provides an overview of carcinogenesis and principles of chemoprevention and highlights certain developments in the past year that exemplify the experience and progress in this area.
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PMID:Progress in chemoprevention of gastrointestinal cancers. 183 93

The mouse Ha-ras oncogene is activated by point mutation and overexpressed in developing papillomas during two-stage skin carcinogenesis in SENCAR mice. One of our research aims is to characterize the factors regulating Ha-ras gene expression at the transcriptional level in SENCAR mouse epidermis. Towards this goal, we sequenced 1400 bp of the 5' upstream region of the mouse Ha-ras gene so as to characterize various cis-regulatory elements present in the gene. We identified seven sites with the proper consensus sequence for binding the SP1 transcription factor and three potential binding sites for the CTF-1 factor. In addition, we located a 13-base sequence with 92% homology to the consensus sequence for an estrogen response element and two hexamers with consensus sequences identical to the core sequence of the glucocorticoid response element. A series of transient gene expression vectors was constructed in which various regions of the mouse Ha-ras 5' upstream region were fused to the chloramphenicol acetyltransferase (CAT) gene. These expression plasmids were transfected into newborn and adult primary SENCAR epidermal cells, the epidermal cell population that presumably contains the stem cells involved in two-stage skin tumorigenesis. Transient gene expression assays carried out after 48-72 h indicated that a 2.3-kb Ha-ras 5' fragment produced CAT activity comparable to that produced by pSV2CAT and pdolCMVCAT, both of which are plasmids with strong viral promoters and enhancers driving CAT gene expression. Maintenance of transfected keratinocytes under both nondifferentiating (0.05 mM calcium) and differentiating (1.2 mM calcium) culture conditions demonstrated that the mouse Ha-ras upstream region was relatively unresponsive to changes in calcium concentration in transient expression assays carried out in either newborn or adult keratinocytes. Our results demonstrated the power of the cloned mouse Ha-ras promoter and upstream region in driving transient gene expression after transfection into primary keratinocytes.
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PMID:Transient expression of the cloned mouse c-Ha-ras 5' upstream region in transfected primary SENCAR mouse keratinocytes demonstrates its power as a promoter element. 191 Apr 81

Acidic and basic fibroblast growth factors (FGFs) are members of a family of proteins that are broad-spectrum mitogens, have diverse hormone-like activities, and function in tumorigenesis. FGF's ability to raise the concentration of intracellular calcium ion suggests that FGF could induce the synthesis of endothelium-derived relaxing factor (EDRF) and consequently vasodilation. Systemic administration of FGF decreased arterial blood pressure. This effect was mediated by EDRF and by adenosine triphosphate-sensitive potassium ion channels. The hypotensive effect of FGF was segregated from its mitogenic activity by protein engineering. These results extend the range of FGF autocrine activities and potential therapeutic applications, emphasize the role of endothelium as an arterial blood pressure--regulating organ, and provide insight on the structural basis of FGF functions.
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PMID:Hypotensive activity of fibroblast growth factor. 195 72


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