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)

Transplantable mouse melanomas possess a melanotropin-sensitive adenylate cyclase system which is responsive to alpha-melanotropin, beta-melanotropin, adrenocorticotropin (ACTH) and prostaglandin E1. It was found that sensitivity to ACTH was not directed towards the ACTH activity but to the intrinsic melanotropin activity of the ACTH molecule. Therefore, the melanotropin-sensitive adenylate cyclase system is hormonally specific to the intrinsic melanotropin activity of peptide hormones and is unique in the melanoma tissue. The significance of the sensitivity to prostaglandin E1 is obscure at present. The melanotropin-sensitive adenylate cyclase requires the presence of Mg2+ or Mn2+, for its enzymic activity. Ca2+ inhibit the enzyme in the presence of a wide range of concentrations of Mg2+. The enzymic activity is ATP concentration-dependent and the saturation concentration appears to be 1 mM. The enzyme is very labile in the unfractionated tumor homogenates. A washed 11000 X g particulate fraction, representing about 30-60% of the total enzymic activity, was found to be more stable and could be stored at 5 degrees C for 2 h without appreciable loss of the activity. This fraction retained sensitivity to melanotropin, prostaglandin E1 and NaF. About 20% of the activity of the tumor homogenate could not be sedimented by centrifugation at 105000 X g for 60 min. This "soluble" fraction was not responsive to melanotropin, prostaglandin E1 and NaF and might be a degradative product produced by the fractionation. Cyclic AMP and alpha-melanotropin were able to increase the tyrosinase activity of isolated mouse melanoma-cells in vitro under the same conditions.
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PMID:PHrmonal specificity of the melanotropin-sensitive adenylate cyclase of mouse melanoma and effect of cyclic AMP on the tyrosinase activity of mouse melanoma cells, in vitro. 0 31

Adenylate cyclase activity as well as intracellular content of sAMP were decreased 2.5-4-fold, as compared with normal state, in plasmatic membranes (PM) of hepatoma 22 and of Ehrlich ascites carcinoma--the tumors characterized by high level- of malignancy. Activity of cAMP phosphodiesterase exceeded distinctly the normal value in all the tumors studied. In less malignant hepatoma 48 the adenylate cyclase activity and content of cAMP were similar to those found in normal liver cells. The guanylate cyclase activity did not differ markedly from values found in normal liver cells in PM of all the tumors studied and in liver tissue of the tumor-bearing animals. Distinct alterations were not found in content of cGMP in the tumors, except of hepatomas 60 and 22, in which the nucleotide level exceeded 2-fold the normal value. The ratio cAMP/cGMP was decreased in the most malignant tumors. At the same time, the ratio was distinctly elevated in tumors with the middle level of malignancy (hepatomas 60 and 61).
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PMID:[Concentration of cyclic nucleotides, activity of adenylate cyclase, 3',5'-AMP phosphodiesterase and guanylate cyclase in plasma membranes from liver and hepatomas of different degrees of malignancy]. 3 Feb 12

Giant cell tumors of bone obtained from 7 patients were dispersed with clostridial collagenase and trypsin and adherent cells were maintained in culture. Early cultures contained both mononucleated and multinucleated cells presumably derived from the stromal and giant cells of the original tumor. The original multinucleated cells did not survive for greater than 7-10 days whereas the mononucleated cells persisted and could be passaged by trypsinization. In 5 of 7 early cultures exposed to parathyroid hormone (PTH) there was a rise in cAMP within 5-10 min in both cells and medium which averaged approximately 12-fold. None of the cells responded to calcitonin and a variable rise in cAMP was seen after incubation with prostaglandin E2. In cells cultured from 3 tumors the PTH response disappeared with passage of the cells, but in the remaining 2, PTH response persisted through multiple passages. The presence as well as the magnitude of the PTH-induced cAMP response in these cells is consistent with a skeletal origin.
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PMID:Response to hormones of cells cultured from human giant cell tumors of bone. 8

The adenosine-3, 5-cyclic monophosphate phosphodiesterase (cPDE) activity in the homogenates of 6 spontaneously metastasizing, nonimmunogenic, glycocalyx-shedding rat mammary carcinomas (MT) was assayed and compared with four histologically and growth rate-matched nonmetastasizing, immunogenic MT. The levels of this enzyme were 2.5 times higher in the nonmetastasizing tumors. To rule out the possibility of the presence of inhibitor(s) or stimulator(s) of cPDE, homogenates from a nonmetastasizing and from a widely metastasizing tumor were mixed. cPDE from both nonmetastasizing and metastasizing MT showed two apparent Km and two corresponding Vmax. The activity of the enzyme at concentrations of 1 muM (low Km) and 100 muM (high Km) adenosine-3, 5-cyclic monophosphate (cAMP) decreased in parallel with increasing metastasizing capacity. About 50% of the low and the high Km cPDE was in the cytosol in both groups, whereas the rest was particulate. The proportion of low and high Km activity was similar in all the fractions except in the plasma membrane of the metastasizing tumors where the percent of low Km enzyme was three times higher than that of the high Km. The steady-state levels of cAMP were 1.3-2.0 times higher in the metastasizing tumors, inversely proportional to their cPDE activities.
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PMID:Adenosine-3',5'-cyclic monophosphate levels and adenosine-3',5'-cyclic monophosphate phosphodiesterase activity in metastasizing and nonmetastasizing rat mammary carcinomas. 16 15

A variety of compounds were assessed for their ability to induce morphological differentiation and to affect the synthesis of RNA in uncloned mouse neuroblastoma cells in culture. The stimulation of morphological differentiation in uncloned cells after exposure for 48 hours to concentrations of 3 times 10-7 to 3 times 10-4 M papavarine or 10-9 to 10-3 M dibutyryl adenosine 3':5'-monophosphate (dibutyryl-cAMP) was associated, in part, with a concentration-dependent decrease in incorporation of [5-3H]uridine into ribosomal RNA (rRNA) and heterogeneous RNA (HnRNA). The latter effect on cellular RNA produced by papavarine occurred within 1 hour after its addition to the medium and was associated with impaired uptake of radioactive precursor into uridine nucleotides and reduction in the intracellular concentration of uridine 5'-triphosphate (UTP). Dibutytyl-cAMP produced a decreased in the specific radioactivity of UTP without affecting the concentration of UTP in the tumor cells. The effects of papavarine and dibutyryl-cAMP could be distinguished further by the 50% reduction of acetylcholinesterase activity produced by papavarine, but not by dibutyryl-cAMP. Papavarine did not, however, reduce the cellular level of the soluble enzyme, adenine phosphoribosyltransferase. Sodium butyrate, while producing morphological effects similar to those of papavarine and dibutyryl-cAMP at equimolar concentrations, caused no significant changes in the incorporation of [5-3H]uridine into rRNA and HnRNA; however, acetylcholinesterase activity was stimulated 6- to 7-fold above control levels. In contrast to the other differentiating agents examined, addition of 10-9 to 3 times 10-4 M concentrations of cAMP to the tissue culture medium enhanced morphological differentiation of nueroblastoma cells, and caused a 10- to 20-fold stimulation of the incorporation of [5-3H]uridine into rRNA and HnRNA at concentrations of 10-4 M and higher. This effect observed only at high concentrations of cyclic nucleotide was accompanied by an elevation in the specific acitivty of UTP, These studies suggest that the morphological response of neuroblastoma cells is not necessarily associated with concomitant alterations in the synthesis of RNA with agents other than cAMP. Observed changes in incorporation of [5-3H]uridine into RNA appear in most instances to be due to alterations in the uptake of uridine, and in the pool size and specific radioactivity of UTP.
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PMID:Effects of adenosine 3':5'-monophosphate and related agents on ribonucleic acid synthesis and morphological differentiation in mouse neuroblastoma cells in culture. 16 51

Six biochemically differentiated clonal lines have been established from a transplantable glioma (tg26) of the C57BL/6 inbred mouse strain. Antibodies have been previously raised against G26 tumor cells, which define a cell surface component(s), NS-1 (nervous system antigen-1), found exclusively in the nervous system. NS-1 concentrations approximate the levels of the original G26 tumor when the clonal lines are grown as clonal tumors in vivo, but are reduced when the cells are grown in vitro. NS-1 concentrations are further reduced in vitro upon incubation of the cells with 1 mM dibutyryl 3:5-cyclic AMP. H-2 histocompatibility antigen concentration, in contrast, is unaffected by dibutyryl cAMP. In addition to expressing NS-1, the neuroectodermal origin of these cell lines is further confirmed by their synthesis of the nervous system specific acidic protein S-100 and by the high specific activity of the enzyme 2:3-cyclic nucleotide 3-phosphohydrolase. In addition, they respond to catecholamines by the elevation of intracellular 3:5-cyclic AMP levels. Whereas expression of S-100 protein is high under in vitro conditions but negligible after one passage in vivo, 2:3-cyclic nucleotide 3-phosphohydrolase is not detectable in vitro but becomes detectable again in vivo. The two membrane-bound constituents, NS-1 and 2:3-cyclic nucleotide 3-phosphohydrolase, therefore seem to be subjected to different regulatory mechanisms from that of the soluble, intracellular S-100 protein.
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PMID:Biochemically differentiated mouse glial lines carrying a nervous system specific cell surface antigen (NS-1). 16 83

An insulin-producing islet cell tumor of the Syrian hamster has been studied in vitro for its capacity to respond to known stimuli of insulin release. Insulin secretion during short term incubation and perifusion of fragments of tumor was detected by radioimmunoassay. Insulin release was increased 2-4 fold by 40 mM potassium in the presence of calcium, glucose (22 mM), glucagon (0.3-3.0 muM), N6,02'-dibutyryl adenosine 3',5'-monophosphate (cAMP; 6mM), and theophylline (10 mM). Concentrations of glucagon that induced insulin release were also effective in activating adenylate cyclase in the membranes of tumor cells. Thus, this tumor appears to possess a cAMP-mediated mechanism for insulin release. Somatostatin (0.8-25 mum) inhibited glucagon-induced insulin release without altering basal or glucagon stimulated adenylate cyclase activity. It would appear that inhibition of glucagon induced insulin release by somatostatin is not mediated by adenylate cyclase. We propose that insulin release by this tumor is sufficiently similar to that found in normal islets so as to make it a suitable model for biochemical studies that require large quantities of homogeneous tissue.
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PMID:Regulation of in vitro insulin release from a transplantable Syrian hamster insulinoma. 16 25

Addition of insulin to cultured mouse plasma tumor cells (MPC-11) increases the entry of tritiated cyclic adenosine 3',5'-monophosphate (3H-cAMP). No increase of entry of N6-O2-dibutyryl adenosine 3',5' cyclic monophosphate (DBcAMP), 5' adenosine monophosphate (5' AMP) or adenosine was noted in the presence of insulin. The stimulation of cAMP transport by insulin was concentration dependent and inactivated insulin had no effect on nucleotide transport. Intracellular radioactivity after transport of cAMP was largely 5'AMP, while most of the extracellular radioactivity remained as cAMP after incubation.
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PMID:Effect of insulin on metabolism of cyclic adenosine 3',5'-monophosphate by plasma cell tumor (MPC-11). 17 58

Studies of TSH release and production were performed in short term monolayer cultures of transplantable, thyroid hormone responsive, thyrotropin (TSH) producing mouse pituitary tumors. These tumors contained large amounts of TSH, small amounts of growth hormone (GH) and no detectable luteinizing hormone (LH), indicating that the predominant hormone product of tumor cells was TSH. The TSH content per tumor cell was similar to that of the normal pituitary where thyrotrophs represent a small fraction of the total cells, suggesting that the TSH content per tumor cell was less than that of the normal thyrotroph. There was a time dependent release and production of TSH by tumor cells in monolayer culture. Thyrotropin releasing hormone (TRH) increased the release into the media and the production of TSH in a dose dependent manner. Maximum effects were noted at 0.2 ng/ml. Thyroid hormones and somatostatin inhibited both basal and TRH induced effects on both TSH release and production. TSH release as induced by TRH was calcium dependent. TSH release was stimulated by ouabain (10(-3)M) and potassium (57 mM), agents known to promote cellular calcium uptake in a calcium dependent manner. These studies indicate that tumor derived cells function in monolayer culture in a similar fashion to normal thyrotrophs. Studies were conducted to test the hypothesis that TRH action is mediated by adenosine 3',5' monophosphate (cAMP). Dibutyryl cAMP (6 mM) and theophylline (10 mM) increased TSH release suggesting that cAMP is involved in TSH release. However, TRH had no detectable effect on tumor cell adenylate cyclase activity or levels of cAMP. In contrast, PGE1 (1-10 mug/ml) stimulated adenylate cyclase activity and elevated cellular levels of cAMP without increasing TSH release. Thus, we are unable to confirm the postulate that cAMP is the intracellular mediator of TRH action.
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PMID:Regulation of thyrotropin (TSH) release and production in monolayer cultures of transplantable TSH-producing mouse tumors. 17 85

The protein kinase activities of a transplantable, insulin-producing hamster islet cell tumor were characterized using gel filtration, sucrose density gradient centrifugation and acrylamide gel electrophoresis. The post-microsomal supernatant fluid contains 70-80% of the protein kinase activity present in crude homogenates. A cAMP-dependent protein kinase, PK I (Mr 170,000), represents 25% of the soluble protein kinase activity assayed with protamine as substrate. It dissociates in the presence of cAMP into a cAMP-binding protein, R2 (Mr 90,000) and a catalytic subunit C (Mr 33,000). The dissociation induced by cAMP seems to be facilitated by the addition of Mg2+ and ATP. The regulatory subunit, R2, changes its gel filtration pattern in the presence of 0.5 M NaCl suggesting dissociation into a smaller subunit, R1 (Mr 44,000). By analogy with purified beef heart protein kinase (Erlichman et al., 1973) and skeletal muscle protein kinase, PK I. The presence in crude homogenates of a free cAMP-binding protein indistinguishable from the R2 derived by dissociation of PK I, suggests that PK I is partially dissociated in vivo. A cAMP-independent (casein) kinase (Mr 210,000) elutes with PK I on columns of Sepharose 6B. Another cAMP-independent protein kinase, PK II (Mr 88,000), is the predominatn form of soluble protein kinase accounting for approximately 75% of the soluble protein kinase activity detected using protaimine as substrate. This cAMP-independent protein kinase changes its gel filtration pattern in the presence of 0.5 M NaCl giving rise to a form which appears to have the same Mr (33,000) as the catalytic subunit of PK I. Studies comparing the catalytic subunit C of PK I with PK II and its salt-induced smaller molecular form demonstrate facile association of C with the cAMP-binding protein of purified bovine heart protein kinase to yield a hybrid holoenzyme, whereas PK II and its smaller form fail to recombine in this fashion. The 33,000 dalton forms derived from PK I (by cAMP) and PK II (by salt) also show different substrate specificities. It would appear, therefore, that pK II is a cAMP-independent protein kinase unrelated to PK I.
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PMID:Characterization of the protein kinases in a transplantable islet cell tumor of the Syrian hamster. 17 65


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