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:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cases were presented to describe the clinical manifestations, histological features, and diagnostic criteria about the current classification of ovarian tumors. They included peritoneal serous borderline tumor, endocervical-like the intestinal-type mucinous borderline tumor, transitional cell carcinoma of ovarian surface epithelial-stromal tumors and juvenile granulosa cell tumor, sclerosing stromal tumor, hepatoid yolk sac tumor, and primary mucinous carcinoid tumor of non-surface epithelial ovarian tumors. Cases were also presented for discussing the significance of structures and features of some ovarian tumors which have been reevaluated and newly classified. For instance, tumor cell of granulosa cell tumor gives vimentin expression, but is unable to express cytokeratin in all the cases detected with monoclonal antibody of CK-2. Based on the clinical manifestations, exact locating site in the ovary, as well as the histology and histochemistry features, it is possible to identify the stromal luteoma, leydig cell tumor, and non-specific steroid cell tumor respectively in the family of steroid cell tumors. Additionally, the diagnostic significance of the occurrence of basal membrane-like substance and intestinal cells in some yolk sac tumors is also discussed.
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PMID:[Pathological observation on the new classification and features of ovarian tumors]. 129 22

5-hydroxytryptamine (5-HT) is a mitogen for fibroblasts, vascular smooth muscle cells, renal mesangial cells, and jejunal crypt cells. The human carcinoid cell line (termed BON) that we established in our laboratory from a pancreatic carcinoid tumor produces and secretes 5-HT. In this study, therefore, we examined the effect of 5-HT on growth of BON cells. Furthermore, by use of selective 5-HT receptor antagonists, we examined receptor and post-receptor mechanisms by which 5-HT-induced responses were produced. 5-HT stimulated growth of BON cells. 5-HT stimulated phosphatidylinositol (PI) hydrolysis in a dose-dependent fashion and inhibited cyclic AMP production in a dose-dependent fashion. The 5-HT1A/1B receptor antagonist, SDZ 21-009, prevented the reduction of cyclic AMP production evoked by 5-HT and inhibited the mitogenic action of 5-HT. The 5-HT1C/2 receptor antagonist, mesulergine, competitively inhibited PI hydrolysis, but did not affect the mitogenic action of 5-HT. The mitogenic action of 5-HT and the reduction of cyclic AMP production evoked by 5-HT were also inhibited by pertussis toxin. These results suggest that 5-HT is an autocrine growth factor for BON cells and that mitogenic mechanism of 5-HT involves receptor-mediated inhibition of the production of cyclic AMP which may be linked to pertussis toxin-sensitive GTP binding protein. 8-bromo-cyclic AMP inhibited growth of BON cells whereas 8-bromo-cyclic GMP had no effect on cell growth. Involvement of protein kinase A in BON cell growth regulation was confirmed by the observation that a cAMP-dependent protein kinase antagonist (Rp-cAMPS) could stimulate BON cell growth.
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PMID:Receptor-mediated autocrine growth-stimulatory effect of 5-hydroxytryptamine on cultured human pancreatic carcinoid cells. 130 21

P68 is a protein kinase expressed by eukaryotic cells, which is inducible by alpha interferon, and is believed to be an important factor in the regulation of viral and cellular protein synthesis. We have previously reported on a monoclonal antibody, TJ4C4, which is able to specifically detect p68 in formalin-fixed, paraffin-embedded tissue. Because of its important role in regulating cellular protein synthesis, we hypothesized that p68 expression would vary among lung neoplasms with level of differentiation and degree of biosynthetic activity. A total of 246 untreated primary pulmonary and pleural neoplasms were studied. The frequency and relative intensity of p68 expression was determined by light microscopic evaluation of ABC immunoperoxidase stained specimens. All categories of tumors studied demonstrated a spectrum of p68 expression. Expression of p68 correlated well with degree of differentiation in squamous cell carcinomas (SQCC) and acinar adenocarcinomas (AAC). Papillary adenocarcinoma (PAC) and bronchioalveolar carcinoma (BAC) expressed low levels of p68, despite their well differentiated appearance. Expression of the antigen in large cell carcinoma (LCC) was higher than that seen in either poorly differentiated AAC or SQCC. Neuroendocrine tumors generally showed low levels of p68 expression with the intermediate variant of small cell carcinoma expressing higher levels of p68 than the classic "oat cell" form (SCC). Carcinoid tumors expressed higher levels of p68 than did atypical carcinoid tumors. Mesotheliomas showed weak expression of p68, limited primarily to areas of glandular differentiation in the epithelioid form.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Expression of the protein kinase p-68 recognized by the monoclonal antibody TJ4C4 in human lung neoplasms. 135 15

The objective of these experiments was to investigate the influence of activation of three second messenger systems (protein kinase-C, adenylate cyclase-cAMP, and calcium mobilization) on the secretion of pancreastatin (PST) and chromogranin-A (CGA) by a human pancreatic carcinoid cell line (BON) in tissue culture. Stimulation of protein kinase-C by a phorbol ester (0.025-7.5 microM) caused a significant dose-related release of PST (186 +/- 22-4271 +/- 228% over controls). Treatment of BON cells with graded doses of 8-bromo-cAMP (0.14-3.0 mM) and isobutylmethylxanthine (IBMX; 0.01-1.0 mM) also stimulated a dose-related release of PST (107 +/- 22-284 +/- 28 and 16 +/- 12-1076 +/- 100% over controls, respectively). Incubation of BON cells with ionomycin (0.134-13.4 microM) increased the release of PST (102 +/- 15-554 +/- 21% over controls) in a dose-related manner. A combination of IBMX and ionomycin resulted in an additive effect, whereas treatment with a phorbol ester plus IBMX resulted in a synergistic effect on PST release. Pretreatment of BON cells with monensin, an agent that prevents processing of precursors to smaller peptides, significantly decreased PST, but not CGA, secretion in response to phorbol ester or ionomycin. These findings indicate that protein kinase-C, cAMP, and Ca2+ mobilization participate in CGA and PST secretion. Although the observation that secretions of PST and CGA in response to theophylline are quantitatively associated, the absence of a quantitative relationship in the release patterns of PST and CGA in response to phorbol ester and ionomycin do not support a simple precursor-product relationship between CGA and PST. The monensin experiments are consistent with the notion that PST is derived from CGA in BON cells.
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PMID:Regulation of pancreastatin release from a human pancreatic carcinoid cell line in vitro. 170

Five monoclonal antibodies recognizing different keratin polypeptides in immunoblotting or different epithelial cell types in complex tissues were studied for their suitability as reagents for the differential diagnosis of primary and secondary malignant epithelial liver tumors. The broad specificity keratin antibodies lu-5 and KL-1 stained all epithelial liver neoplasms. In contrast the antibodies CK-7 (Ker-7-specific), CK-2 (Ker-18-specific) and KA-4 (Ker-19-specific in liver) allow these neoplasms to be divided into three groups: Hepatocellular carcinomas were CK-2-positive and CK-7-negative. Cholangiocellular carcinomas, liver metastases of extrahepatic bile duct carcinomas, liver metastases of a ductal carcinoma of breast, and a follicular thyroid carcinoma were stained positively by CK-2, CK-7, and KA-4. In 1 of 6 hepatocellular carcinomas neoplastic hepatocytes were focally labeled by KA-4. In a focal nodular hyperplasia of the liver modified hepatocytes were decorated not only by CK-2 but also by CK-7 and KA-4. Liver metastases of colorectal adenocarcinomas and of a carcinoid tumor were stained positively by CK-2 and KA-4 but not by CK-7.
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PMID:Keratin polypeptides in malignant epithelial liver tumors. Differential diagnostic and histogenetic aspects. 243 41

This was a study of the effects of gastrin on gastric mucosal cyclic-adenosine 3':5'-monophosphate (cAMP)-dependent protein kinase activity and DNA synthesis in rat stomach carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine (MNNG) in order to clarify the mechanism of the enhanced effect of gastrin on the early stage of stomach carcinogenesis. Inbred Basel-Wistar rats received MNNG in drinking water (50 micrograms/ml for 32 weeks) and were treated with s.c. injections of pentagastrin (300 micrograms/kg twice daily for 4 weeks) beginning with the fourth and eighth weeks after the initiation of MNNG treatment. The incidence of gastric adenocarcinoma in fourth-week gastrin-treated rats and of gastric carcinoid in eighth-week gastrin-treated rats was higher than that in rats treated with MNNG alone. The former tumors developed in the antrum and most of the latter tumors in the fundus. In the early stage of carcinogenesis the labeling index [( 3H]thymidine-labeled nuclei/one gland) in both the antrum and fundus was the same in MNNG-plus-gastrin-treated groups and in the MNNG-only-treated group. With regard to the distribution of cAMP-dependent protein kinase isoenzyme in fourth-week gastrin-treated rats, the proportion of type I cAMP-dependent protein kinase significantly increased in the antrum during the eighth week after the initiation of MNNG treatment (P less than 0.01). The increased type I activity in the antrum of the gastrin-treated rats agreed with the high incidence of gastric adenocarcinoma in the antrum. Type I isoenzyme clearly increased in gastric adenocarcinoma. These results suggest that type I cAMP-dependent protein kinase can play an important role in the enhanced effect of gastrin on rat stomach carcinogenesis induced by MNNG.
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PMID:Effect of gastrin on gastric mucosal cyclic adenosine 3':5'-monophosphate-dependent protein kinase activity in rat stomach carcinogenesis induced by N-methyl-N'-nitro-N-nitrosoguanidine. 402 63

The purpose of this study was to investigate the effects of activation of various second messenger signaling systems on gene expression (i.e. mRNA levels) of a peptide hormone processing enzyme called prohormone convertase-1 (PC-1, also called PC-3) in a human pancreatic carcinoid cell line (BON) that expresses several endocrine peptides (chromogranin A, pancreastatin, neurotensin). Pharmacologic activation of adenylate cyclase-cAMP, protein kinase-C and Ca2+ mobilization pathways increased PC-1 mRNA levels and neurotensin secretion. Elevations in PC-1 mRNA levels were dose and time-related. Secretagogue-induced cellular depletion of neurotensin was followed by a replenishment of cellular neurotensin stores and an upregulation of PC-1 mRNA levels. Together, these data indicate that PC-1 mRNA expression is increased with peptide secretion and coordinated with maintenance of cellular stores of peptides.
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PMID:Stimulation of prohormone convertase-1 mRNA expression by second messenger signaling systems. 961 Mar 84

The first step in the biosynthesis of melatonin in the pineal gland is the hydroxylation of tryptophan to 5-hydroxytryptophan. A cDNA of human tryptophan hydroxylase (TPH) was cloned from a library of human pineal gland and expressed in Escherichia coli. This cDNA sequence is identical to the cDNA sequence published from the human carcinoid tissue [1]. This human pineal hydroxylase gene encodes a protein of 444 amino acids and a molecular mass of 51 kDa estimated for the purified enzyme. Tryptophan hydroxylase from human brainstem exhibits high sequence homology (93% identity) with the human pineal hydroxylase. The recombinant tryptophan hydroxylase exists in solution as tetramers. The expressed human pineal tryptophan hydroxylase has a specific activity of 600 nmol/min/mg when measured in the presence of tetrahydrobiopterin and L-tryptophan. The enzyme catalyzes the hydroxylation of tryptophan and phenylalanine at comparable rates. Phosphorylation of the hydroxylase by protein kinase A or calmodulin-dependent kinase II results in the incorporation of 1 mol of phosphate/mol of subunit, but this degree of phosphorylation leads to only a modest (30%) increase in BH(4)-dependent activity when assayed in the presence of 14-3-3. Rapid scanning ultraviolet spectroscopy has revealed the formation of the transient intermediate compound, 4alpha-hydroxytetrahydrobiopterin, during the hydroxylation of either tryptophan or phenylalanine catalyzed by the recombinant pineal TPH.
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PMID:Cloning and expression of recombinant human pineal tryptophan hydroxylase in Escherichia coli: purification and characterization of the cloned enzyme. 1052 50

Background Insulin-like growth factor 1 (IGF-1) is an autocrine regulator of carcinoid tumors. Blockade of IGF-1 signaling has been proposed as a therapeutic target in the treatment of patients with carcinoid syndrome. We hypothesized that the induction of parallel raf-1/MEK1 pathways will block IGF-1-mediated chromogranin A (CgA) maintenance. Methods Human gastrointestinal carcinoid tumor cells (BON) were treated with IGF-1 (0-500 ng/mL). Raf-1/MEK1 activation was achieved with an estrogen-inducible raf-1 vector that was transduced into BON cells. Activation of IGF-1/raf-1 pathways was determined by phosphorylation of downstream targets p70s6 and ERK1/2. The secreted and intercellular levels of CgA were measured in conditioned media and whole cell extracts by Western and enzyme-linked immunosorbent assay analysis. Results IGF-1 and raf-1 pathways were activated successfully in BON cells, as shown by high levels of phosphorylated p70s6 and phosphorylated ERK1/2, respectively. Treatment of BON cells with IGF-1 stimulated the release of CgA, while high intracellular CgA levels were maintained. The activation of raf-1/MEK1 reversed the effect of IGF-1 treatment by the depletion of intracellular CgA. Conclusions The induction of the raf-1/MEK1 pathway blocks IGF-1-mediated intracellular neuroendocrine hormone regulation. Therefore, raf-1/MEK1 activation may be a viable method to block IGF-1-mediated cellular effects and serve as a therapeutic target in gastrointestinal carcinoid tumors.
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PMID:Insulin-like growth factor 1 signaling in human gastrointestinal carcinoid tumor cells. 1565 90

Neuroendocrine tumors, such as carcinoids, are highly metastatic neoplasms that secrete bioactive hormones resulting in carcinoid syndrome. Few curative treatments exist outside of surgical resection. We have previously shown that activation of the Raf-1 signaling pathway can suppress hormone production in carcinoid tumor cells. In this study, we investigated a novel treatment for carcinoid tumor cell growth based on pharmacologic Raf-1 activation using the compound ZM336372. Treatment of carcinoid tumor cells with ZM336372 resulted in progressive phosphorylation of Raf-1, mitogen-activated protein kinase 1/2, and extracellular signal-regulated kinase 1/2. Importantly, exposure to ZM336372 resulted in a significant reduction of bioactive hormone levels as well as the transcription factor, human achaete-scute homologue-1 in carcinoid tumor cells. Furthermore, treatment with ZM336372 led to a marked suppression of cellular proliferation and induction of the cell cycle inhibitors p21 and p18. In summary, ZM336372 targets both proliferation and palliative issues associated with carcinoid tumor cells, and therefore, warrants further investigation as a possible therapeutic strategy for patients with carcinoid tumors.
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PMID:ZM336372, a Raf-1 activator, suppresses growth and neuroendocrine hormone levels in carcinoid tumor cells. 1595 48


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