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)

Dimethylbenzanthracene-induced rat carcinomas possess activities binding cyclic adenosine 3':5'-monophosphate (cAMP) and estrogen. When dimethylbenzanthracene-induced tumors regress after ovariectomy of the host, a change in the specific binding of cAMP and estrogen occurs in the tumors. Six days after ovariectomy, cAMP binding increases 5-fold in the nuclei and 2-fold in the cytosol of tumors, while nuclear and cytoplasmic estrogen binding decreases by 80% and 50%, respectively. These changes in activities binding cAMP and estrogen are detectable within 1 day after ovariectomy and the changes are reversed when resumption of tumor growth is induced by the injection of 17beta-estradiol. When dimethylbenzanthracene-induced tumors fail to regress after ovariectomy, the change in activities binding cAMP and estrogen does not occur. Significant increases in the cAMP level as well as in adenylate cyclase and cAMP-phosphodiesterase activities are also found in the regressing tumors. Concomitant with the increase of cAMP-binding activity is an increase in histone kinase activity in the regressing tumor. These data suggest the involvement of cAMP in the growth control of a hormone-dependent mammary rumor.
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PMID:Cyclic AMP-binding proteins: inverse relationship with estrogen-receptors in hormone-dependent mammary tumor regression. 20 18

Our results demonstrate that adrenocorticotropin (ACTH)-induced refractoriness occurs in cultured adrenal tumor cells. Cells became 85% refractory to ACTH-induced cyclic AMP formation in 20 min and the effect persisted if the hormone remained in the incubation medium. Refractory cells gradually regained hormone-specific responsiveness within 24 h if cultures were incubated in fresh media containing serum. The observed effect is hormone specific since cyclic AMP could not induce unresponsiveness to ACTH. The addition of ACTH plus inhibitors of protein synthesis partially reversed hormone-specific refractoriness. However, preincubation with cycloheximide or diphtheria toxin led to superinduction of ACTH-induced cyclic AMP formation. These experiments suggest that unresponsiveness, following hormonal activation of adrenal cells, may be related to a decrease in hormone-specific binding sites or to synthesis of an adenylate cyclase inhibitor.
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PMID:Adrenocorticotropin-induced unresponsiveness in cultured adrenal tumor cells. 20 44

The role of the cyclic AMP-protein kinase system in mediating the steroidogenic effect of ACTH, prostaglandin E1 and dibutyryl cyclic AMP, induced similar stimulations of protein kinase activity, cyclic AMP was studied using human adrenal cells isolated from normal and adrenocortical secreting tumors. At high concentrations of ACTH, complete activation of protein kinase of normal adrenal cells was observed within 3 min, at the time when cyclic AMP production was slightly increased and there was still no stimulation of steroidogenesis. At supramaximal concentrations, ACTH, PGE1 and dibutyryl cyclic AMP and cortisol productions in adrenal cells isolated from normal and from one adrenocortical tumor. In one tumor in which the adenylate cyclase activity was insensitive to ACTH, the hormone was unable to stimulate protein kinase or steroidogenesis, but the cells responded to both PGE1 and dibutyryl cyclic AMP. In another tumor in which the adenylate cyclase was insensitive to PGE1, this compound also did not increase protein kinase activity or steroidogenesis, but both parameters were stimulated by ACTH and dibutyryl cyclic AMP. After incubation of normal adrenal cells with increasing concentrations of ACTH (0.01-100 nM) marked differences were found between cyclic AMP formation and cortisol production. However at the lowest concentrations of ACTH exerting an effect on steroid production a close linked correlation was found between protein kinase activation and cortisol production, but half-maximal and maximal cortisol production occurs at lower concentration of ACTH than was necessary to induce the same stimulation of protein kinase. Similar findings were found after incubating the adrenal cells with dibutyryl cyclic AMP (0.01-10 mM). The results implicate an important role of the cyclic AMP-protein kinase system during activation of adrenal cell steroidogenesis by low concentrations of steroidogenic compounds.
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PMID:Role of cyclic AMP and protein kinase on the steroidogenic action of ACTH, prostaglandin E1 and dibutyryl cyclic AMP in normal adrenal cells and adrenal tumor cells from humans. 21 68

We have studied cAMP metabolism in rat livers undergoing carcinogenesis induced by dietary 3'-methyl-4-dimethylaminoazobenzene. A correlation between the biochemical and the histological changes described in the companion paper has been made. In this study, we saw 100% incidence of cholangiocarcinoma by 10 weeks. During weeks 1--10, the biochemistry of tumor-free areas of the livers only was studied; during weeks 11-13, the increased size of the tumors made possible a biochemical study of the tumor tissue as well as the non-tumor tissue, and a comparison between the two was made. Alterations in all parameters of cAMP metabolism were seen from the earliest stages of treatemnt. Most striking were those of adenylate cyclase activity which preceded and accompanied tumor formation, and were seen in both non-tumor and tumor tissue. In the first few weeks of treatment, small acidophilic glycogen-deficient hepatocytes appeared in the periportal areas of the liver lobules. During this time, there was an increase in maximal isoproterenol stimulation of adenylate cyclase and to a lesser extent in the basal activity of the enzyme; increases in phosphodiesterase activity were seen, and were greatest in weeks 1, 2; cAMP levels were diminished in weeks 1, 2 and slightly but not significantly elevated at week 3. From week 4 onwards an even smaller glycogen-deficient cell population appeared in perilobular areas amongst the acidophilic hepatocytes, and tumors began to appear elsewhere in the livers; at this time, there were further marked increases in the basal activity and isoproterenol responsiveness of adenylate cyclase, and the appearance of increased Gpp(NH)p responsiveness of the enzyme; the increase in phosphodiesterase activities seen at week 3 (smaller than that seen in weeks 1, 2) was sustained but did not further increase; cAMP levels were now significantly elevated also, but they did not rise steadily as did the activity of adenylate cyclase. There was a marked difference between the adenylate cyclase activities in non-tumor tissue from tumor-bearing and non-tumor-bearing livers in weeks 4--10, but there was no difference between the phosphodiesterase activities or cAMP levels in these two groups. Adenylate cyclase activity was extremely high in both non-tumor tissue of tumor-bearing livers from weeks 4--10 and tumors from weeks 11--13. Although phosphodiesterase activities were most elevated in the tumors, there were extremely high cyclic AMP levels in these tissues. The difference between the cAMP levels of tumor and non-tumor tissue was striking. Our findings are discussed with respect to the two-state model of carcinogenesis...
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PMID:A study of cyclic nucleotide metabolism and the histology of rat liver during 3'-methyl-4-dimethylamino-azobenzene carcinogenesis. II. Cyclic AMP metabolism. 21 95

A well-differentiated ductal adenocarcinoma of the Syrian golden hamster induced by N-nitrosobis(2-oxopropyl)amine was transplantable to both nude mice and inbred Syrian hamsters. The tumor grew rapidly in the nude mouse (12-fold increase in size at 45 days) in contrast to its growth in hamster (3-fold increase in size at 45 days). A curious finding associated with the slow-growing tumor in the hamster was an intense infiltration of the neoplasm by polymorphonuclear leukocytes unattended by either necrosis or infection. The neoplasm produced mucin and rapidly and specifically bound 125I-labeled secretin, although the degree of nonspecific binding (40.5%) was higher than that of control hamster pancreas (23%). Unstimulated adenyl cyclase activity (pmol cyclic adenosine 3':5'-monophosphate per mg protein) of the neoplasm was significantly higher [3.76 +/- 0.55 (S.E.)] than that of unstimulated normal hamster pancreas (1.03 +/- 0.44). Secretin did not significantly change the level of cyclic adenosine 3':5'-monophosphate (3.3 +/- 0.56) from the unstimulated level in the neoplasm, in contrast to its effect on normal pancreas where the level was increased 3-fold (3.1 +/- 0.75).
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PMID:Transplantable ductal adenocarcinoma of the Syrian hamster pancreas. 21 89

The existence of aminergic receptors in mouse Ehrlich ascites tumor cells was studied. L-Isoproterenol in vitro stimulated the formation of cAMP in isolated Ehrlich ascites tumor cells. Stimulation by isoproterenol of cAMP formation was not significantly inhibited by practolol, a beta1-adrenoceptor antagonist-Salbutamol, a beta2-adrenoceptor agonist, markedly stimulated the formation of cAMP in Ehrlich ascites tumor cells at concentrations from 10(-8)-10(-3) M. After the addition of salbutamol, cAMP levels reached a maximum in 10 min and declined to about 2-fold of the basal level to 30 min. The stimulation by salbutamol of cAMP formation was markedly inhibited by butoxamine, a beta2-adrenoceptor antagonist, but not by practolol. Furthermore, the effect of a maximal dose of salbutamol was additive to that of prostaglandin E2. Histamine and 4-methylhistamine, a histamine H2 receptor agonist, had no significant effects. Therefore, it is suggested that a beta2-adrenergic receptor exists in the membranes of Ehrlich ascites tumor cells in terms of the adenylate cyclase-cAMP system.
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PMID:Evidence for activation by beta2-adrenergic receptors of adenosine 3',5'-monophosphate formation in Ehrlich ascites tumor cells. 21 68

Implantation of MtT-F4 tumor, a mammotropic tumor that secretes large quantities of ACTH, GH and prolactin, into male Fisher rats induced the development of hyperlipidemia. Free fatty acid, triglyceride and cholesterol levels in the plasma were significantly increased at 31 days after tumor implantation. Blood glucose and glycerol levels remained normal, while uric acid concentration in the blood was significantly decreased. The lipolytic response of isolated adipose tissue cells to ACTH was significantly higher in cells derived from rats bearing an MtT-F4 tumor for 31 days than from their corresponding controls. However, the activity of adenylate cyclase in fat cells stimulated with ACTH was not significantly higher in cells derived from tumor bearing rats than in cells from control rats.
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PMID:Development of hyperlipidemia associated with increased lipolytic response of isolated adipose tissue cells following prolonged stimulation by an ectopic pituitary tumor. 21 11

Two groups of mutant clones were isolated from YI adrenocortical tumor cells. One group, Y1(Kin), exhibited altered cytosolic cyclic AMP-dependent protein kinase activity; the second group, Y1(Cyc), exhibited diminished corticotropin-responsive adenylate cyclase activity. Steroidogenic responses to corticotropin and cyclic nucleotides closely paralleled cyclic AMP-dependent protein kinase activity in the Y1(Kin) mutants. In Y1(Cyc) mutants, corticotropin had little effect on steroidogenesis, whereas cyclic nucleotides were fully active. These data imply that adenylate cyclase and cyclic AMP-dependent protein kinase are obligatory components of the corticotropin-stimulated steroidogenic pathway.
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PMID:Mutations in cyclic AMP-dependent protein kinase and corticotropin (ACTH)-sensitive adenylate cyclase affect adrenal steroidogenesis. 22 10

The Ca2+ content of glial tumor (C6) cells was reduced approximately 5-fold by repeated treatment with media containing ethylene glycol bis(beta-aminoethyl ether) N,N'-tetraacetic acid (EGTA) without loss of cellular viability. The ability of the cells to accumulate cAMP in response to beta-adrenergic agonists was reduced 60 to 70% following Ca2+ depletion. Ca2+ did not affect the apparent KACT for norepinephrine, nor did it change the concentration of propranolol required to produce 50% inhibition of the maximal norepinephrine response. Phentolamine did not alter the Ca2+ dependence of the response. The binding of dihydroalprenolol by intact C6 cells was not influenced by Ca2+. Furthermore, pretreatment with norepinephrine did not affect the Ca2+ dependence of cAMP accumulation. The effects of Ca2+, therefore, appeared to be exerted on components of the adenylate cyclase system other than the catecholamine receptor. Micromolar free Ca2+ concentration in the extracellular medium were sufficient to restore a maximal norepinephrine response to Ca2+-depeleted cells. The effect of Ca2+ on cAMP accumulation in response to hormone was immediate and was rapidly reversible upon the addition of EGTA in excess of the cation. Cells in media containing Ca2+ exhibited a characteristic biphasic time course of cAMP accumulation; with Ca2+-depleted cells cAMP was accumulated more slowly and the subsequent decline in cAMP content was also reduced. Verapamil, an inhibitor of plasmalemmal Ca2+ influx, decreased the Ca2+-dependent component of the cAMP accumulation when added prior to the cation. The effect of Ca2+ on cAMP accumulation was reduced more extensively by pretreatment of cells at 45 degrees C under Ca2+-depleted (80% loss) than under Ca2+-restored (30% loss) conditions. Trifluoperazine at micromolar concentrations decreased the Ca2+-dependent increment in accumulation of cAMP in Ca2+-restored cells. This inhibition was not overcome by increasing concentrations of norepinephrine or of extracellular Ca2+.
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PMID:Calcium dependence of hormone-stimulated cAMP accumulation in intact glial tumor cells. 22 32

Two variant cell lines (Y6 and OS3), derived from the ACTH-sensitive mouse adrenocortical tumor clone Y1, are defective in the ACTH-sensitive adenylate cyclase system. This study further characterizes the nature of the defects in Y6 and OS3 cells using ACTH1-10, ACTH4-10, and cholera toxin. In Y1 cells, ACTH1-39, ACTH1-10, and ACTH4-10 stimulated steroidogenesis to the same maximum level with Kd' values of 5 x 10(-11) M, 5 x 10(-7) M and 10(-4) m respectively. ACTH1-10 (0.4 mM) and ACTH4-10 (3.2 mM) increased the accumulation of adenosine 3',5'-monophosphate (cAMP) in Y1 cells two- to three-fold. Cholera toxin increased steroidogenesis and cAMP accumulation in Y1 cells with Kd' values of 0.4 ng/mL and 9 ng/mL respectively. Y6 and OS3 cells responded to added cholera toxin with increased cAMP accumulation and increased steroidogenesis but did not respond to ACTH1-39, ACTH1-10, or ACTH4-10 at concentrations effective in Y1 cells. These data are interpreted to suggest that Y6 and OS3 cells are defective in a process or component that links the principal binding regions of the ACTH receptor to the catalytic subunit of the adenylate cyclase system. Attempts to were made to assess the interactions of ACTH with the principal binding regions of the ACTH receptor by analysis of binding of radioactive, iodinated ACTH1-24. ACTH binding, however, showed low affinity, high capacity, and no target-tissue specificity, and was considered not to be useful in evaluating the integrity of the ACTH receptor.
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PMID:Evaluation of receptor function in ACTH-responsive and ACTH-insensitive adrenal tumor cells. 22 81


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