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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Cyclic AMP may be involved in the modulation of cell growth. The present work sought to further define differences between normal cells and tumor cells in their cyclic AMP system. Mouse embryo fibroblasts and murine bladder transitional epithelium tumor cells were grown in vitro; at various times, adenyl cyclase activity was assayed by measuring the conversion of [alpha32P]ATP to cyclic AM32P; stimulation by prostaglandin E1 or sodium fluoride was also determined. Base line and fluoride-stimulated enzyme activity were significantly greater in normal cells than tumor cells (P less than 0.01), and reached a peak at day 2; at confluency, levels in both systems decreased. Prostaglandin E1-stimulated levels, in contrast, were greater in tumor cells, there being a 10 fold greater relative stimulation in these cells compared to normal cells (P less than 0.01). Findings of a possibly greater sensitivity in these tumor cells may be important in a therapeutic modulation of tumor growth.
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PMID:Differences in adenylate cyclase activities in murine normal cells and bladder tumor cells in tissue culture. 18 32

There is evidence than adenosine 3',5'-monophosphate (cAMP) and guanosine 3',5'-monophosphate (cGMP) may have antagonistic actions on cell growth, with cAMP inhibiting and cGMP stimulating this process. However, reductions in cAMP and increases in cGMP are not charactersitic of all neoplastic tissues. Thus, benign and malignant tissues from hepatoma-bearing rats exposed to the hepatic carcinogen DL-ethionine have elevated rather than depressed cAMP, compared to control liver, and parenteral administration of this drug increases hepatic cAMP within hours. In the present study, the effects of ethionine ingestion on the hepatic content and metabolism of both cAMP and cGMP were examined sequentially in rats at 2 and then 6 wk intervals, from the initiation of drug administration until the development of hepatomas. After 2 wk, cAMP content of quick-frozen liver from rats receiving ethionine (E) was significantly increased (826 +/- 91 pmole/g wet weight) above that of liver from pair-fed controls (C, 415 +/- 44), whether calculated by tissue wet weight, protein, or DNA content. In benign tissue from E, higher cAMP was still evident after in vitro incubations of slices with 2 mM 1-methyl-3-iso-butylxanthine (MIX) and was associated with enhanced adenylate cyclase and unchanged high or low Km cAMP-phosphodiesterase activities. These findings are compatible with accelerated cAMP generation in liver from E. Protein kinase activity ratios were significantly increased in frozen liver from E (0.52 +/- 0.04 versus 0.36 +/- 0.03 in C), and the percent glycogen synthetase in the I form was clearly reduced (19% +/- 2% in E versus 47% +/- 5% in c). incubation of hepatic slices from E or C with MIX and/or 10 muM glucagon further increased cAMP and protein kinase activity ratios, data which imply higher effective, as well as total, cellular cAMP in E. Changes in cAMP metabolism and action observed at 2 wk persisted throughout the 38-wk period of drug ingestion. Adenylate cyclase activity, cAMP content, and protein kinase activity ratios of ethionine-induced hepatomas exceeded those of both the surrounding liver from tumor-bearing rats and that of control liver, but alterations in these parameters were qualitatively similar in both tissues from E. By contrast, while cGMP in quick-frozen surrounding liver from tumor-bearing rats (36 +/- 4 pmole/g wet weight) did not differ from that of control liver (30 +/- 3), cGMP in the hepatomas was increased. This change was evident in both frozen tumor (89 +/- 10) and in tumor slices incubated in vitro with MIX (C, 90 +/- 11; surrounding liver, 85 +/- 10; hepatoma 231 +/- 29). These results indicate that malignant conversion can occur in liver with a sustained elevation of both total and effective cAMP during the premalignant phase. The increase in cGMP detected in ethionine-induced hepatomas could also be a key determinant of malignant transformation in the model, although premalignant changes in cGMP were not apparent.
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PMID:Sequential alterations in the hepatic content and metabolism of cyclic AMP and cyclic GMP induced by DL-ethionine: evidence for malignant transformation of liver with a sustained increase in cyclic AMP. 18 92

In the adrenocortical carcinoma cell, in contrast to normal isolated adrenal cells, 10 to 50 muunits of ACTH do not raise the level of adenosine cyclic 3':5'-monophosphate (cyclic AMP), protein kinase activity, and steroidogenesis. This indicates a lesion in the tumor adenylate cyclase system. Two-tenths to 10 mM cyclic AMP and guanosine cyclic 3':5'-monophosphate (cyclic GMP) which stimulate steroidogenesis in a normal cell, activate protein kinase activity in a concentration-response manner without any detectable rise in steroidogenesis in the adrenocortical carcinoma cell. Cycloheximide and actinomycin D do not inhibit the stimulation of the phosphorylation. These results suggest that the tumor cyclic nucleotide-dependent protein kinase activity is unrelated to steroidogenesis and is also not under the transcriptional or translational control steps. Curiously, muM concentrations of cyclic AMP, in contrast to cyclic GMP, stimulate protein kinase activity. In a normal cell, both cyclic AMP and cyclic GMP, in this concentration range, stimulate protein kinase without an increase in steroidogenesis. It is therefore proposed that, in contrast to the normal cell, there is an additional defect in cyclic GMP-dependent protein kinase.
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PMID:Metabolic regulation and relationship of endogenous protein kinase activity and steroidogenesis in isolated adrenocortical carcinoma cells of the rat. 18 48

Steroidogenesis by Y-1 adrenal tumor cells in culture is stimulated by ATP, adenyl-5'-yl imidodiphosphate (App(NH)), adenosine 5'(beta, alpha-methylene)triphosphate (App(CH2)p), ADP, AMP, NAD, FAD, and adenosine but not by adenine or other nucleoside triphosphates. ATP, App(NH)p, App(CH2)p, and adenosine are active in the micromolar range. Like adrenocorticotropic hormone (ACTH), the onset of stimulation is immediate and occurs to the same extent. Also active are 2'- and 5'-deoxyadenosine and 2-chloroadenosine whereas adenine xyloside, L-riboside, or arabinoside have very low activity. Stimulation is accompanied by rounding of the cells. Dipyridamole, an inhibitor of adenosine transport, increased the response to low concentrations of adenosine, suggesting that adenosine acts externally. Stimulation of steroidogenesis by adenosine or phosphorylated adenosine compounds fails to occur in the presence of crystalline adenosine deaminase, and the effect of the enzyme on adenosine, ATP, or NAD stimulation is reversed by the competitive inhibitor erythro-9-[3-(nonane-2-ol)]adenine. This suggests that the enzyme acts specifically on adenosine and a requirement for the conversion of the above compounds to adenosine seems probable. The inhibition of cAMP effects by adenosine deaminase suggests that some of its effects are also mediated by conversion to adenosine. Similar stimulation is seen in I-10 Leydig tumor cells, but an ACTH-resistant mutant of Y-1 cells, called OS-3, is relatively resistant to adenosine. Adenosine and 2-chloroadenosine stimulate adenylate cyclase in membranes from Y-1 and I-10 cells at concentrations slightly greater than are effective for steroidogenesis. Other nucleosides are ineffective. Like the NH2-terminal 24 residues of adrenocorticotropic hormone (1-24 ACTH), the adenosine effect in Y-1 membranes is rapid and is on the Vmax intercept (versus ATP) and not on the Km. In contrast to steroidogenesis, adenosine is only a partial agonist for adenylate cyclase. It effect occurs in the presence of ITP, GTP, or guanyl-5'-yl imidodiphosphate (Gpp(NH)p). Theophylline inhibits adenosine-stimulated steroidogenesis. Inhibition of adenylate cyclase occurs in the same concentration range but is of the mixed type.
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PMID:Activation of steroidogenesis and adenylate cyclase by adenosine in adrenal and Leydig tumor cells. 18 24

Some of the regulatory mechanisms of cyclic adenosine monophosphate (AMP) production in human brain tumors were investigated by assessing both cyclic AMP levels and adenyl cyclase activity. A large disparity was found between the levels of cyclic AMP of normal brain and brain-tumor tissue. Cyclic AMP levels were much lower in brain tumors (25.8 pmoles (picomoles)/mg protein) than in normal brain (98.8 pmoles/mg protein). These studies also show that the abnormally low levels of cyclic AMP in tumors parallel those of adenyl cyclase. The mean adenyl cyclase activity of brain tissue was found to be 111.0 pmoles of cyclic AMP/min/mg protein, while that of the tumor was only 23.0 pmoles/min/mg protein. Levels of cyclic AMP and adenyl cyclase activity were inversely related to the degree of malignancy. Attempts to stimulate adenyl cyclase in homogenates of human brain and brain tumors resulted in a similar response in both tissues. Norepinephrone was the most effective stimulant and produced a two- to threefold increase in cyclic AMP production, while histamine had no effect. It is concluded that one of the factors governing tumor growth may be a defect in the adenyl cyclase system.
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PMID:Cyclic AMP and adenyl cyclase in brain tumors. 19 76

Gonadotropic hormones are required for the induction and maintenance of tumors arising in ovaries that have been transplanted to the spleens of gonadectomized mice. The characteristics of gonadotropin receptors for human chorionic gonadotropin (HCG)-luteinizing hormone on cells from these tumors of varying size, age, and morphology have been determined. The specific binding of 125I-labeled HCG to cells obtained by collagenase digestion, 15 to 65 weeks postimplantation from granulosa cell or luteinized cell, or mixed granulosa-luteal tumors was analyzed by Scatchard plot. Neither the size, weight, duration of implantation, nor histological morphology affected the receptor-binding affinity [equilibrium dissociation constant (Kd), 6 X 10(-10) M], and, presumably, the receptor is qualitatively similar. In contrast, the number of HCG receptors per cell increased 17-fold and was related to the degree of morphological luteinization of the tumor. HCG-sensitive adenyl cyclase was also demonstrated and compared to HCG binding in a highly luteinized tumor.
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PMID:Gonadotropin receptors in experimentally induced ovarian tumors in mice. 19 83

Fluoride-stimulated adenylate cyclase is demonstrated inisolated tumor cells of transplantable rat pituitary tumor MtT-F4 in vitro. The intracellular cyclic adenosine 3':5'-monophosphate is lowered in the cells incubated in the presence of synthetic somatostatin. Contrary to the findings reported for normal pituitary, however, the immunoreactive growth hormone release does not change when either somatostatin or phosphodiesterase inhibitors are present in the incubation medium. The presence of dibutyryl cyclic adenosine 3':5'-monophosphate (5 mM) in the incubation medium does not change the rate of growth hormone release by isolated tumor cells.
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PMID:Effect of somatostatin on growth hormone release by MtT-F4 rat pituitary tumor in vitro. 19 84

A somatic cell genetic approach was used to study the role of cyclic nucleotides in adrenal steroidogenesis. 8-Bromoadenosine 3',5'-monophosphate (8BrcAMP) stimulated steroidogenesis (K'd=0.1 mM) in cultured mouse adrenocortical tumor cells (Clone Y1). In addition, 8BrcAMP inhibited Y1 cell growth and caused Y1 cell monolayers to assume a rounded morphology. As a consequence, 8BrcAMP (at concentrations greater than or equal to 0.4 mM) reduced the relative plating efficiency of Y1 cells to less than 10(-5). Y1 cells were mutagenized with ethyl methanesulfonate (300 microgram/ml) and grown in the presence of 0.4 mM 8BrcAMP. A surviving colony (8BrcAMPr-1) was shown to be resistant to growth inhibition (relative plating efficiency at 1.0 mM 8BrcAMP=50 percent)) and to morphological changes induced by 8BrcAMP. 8BrcAMPr-1 cells had diminished steroidogenic responses to cyclic nucleotides and to ACTH (less than or equal to 33 percent of maximum). In 8BrcAMP(R)-1 cells, adenylate cyclase activity remained responsive to ACTH, and cyclic AMP phosphodiesterase activity was not increased. These data suggest that 8BrcAMPr-1 cells are defective at a point common to cyclic AMP action on growth, morphology and steroidogenesis. The associated decrease in responsiveness of the steroidogenic pathway to ACTH suggests that ACTH-regulated steroidogenesis is via a cyclic nucleotide-mediated mechanism.
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PMID:Isolation of mutant adrenocortical tumor cells resistant to cyclic nucleotides. 20 May 6

Experiments were conducted to test the hypothesis that intracellular concentrations of guanosine triphosphate (GTP) regulate the activity and hormonal sensitivity of adenylate cyclase in intact cells. By appropriate treatments, the GTP concentrations of Ehrlich ascites tumor cells could be varied between 28% and 680% of control values. Cyclic AMP concentrations were measured before and after addition of epinephrine in cells containing this range of GTP concentratins. Basal cyclic AMP concentrations were unaffected by changes in GTP concentrations. In cells containing lowered concentrations of GTP, the cyclic AMP concentration following addition of epinephrine was half that in control cells. Elevation of GTP concentrations above normal and had no effect on cyclic AMP concentrations following epinephrine treatment.
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PMID:Effects of GTP on cyclic AMP concentrations in intact Ehrlich ascites tumor cells. 20 82

When adenylate cyclase activities in purified membranes from normal rat liver and from a series of rapid growing transplantable Morris hepatomas were examined at various temperatures, several unique features were observed. Two of the hepatomas yielded patterns similar to that of normal liver, even though glucagon did not activate either tumor adenylate cyclase but did activate the normal liver enzyme. The patterns of the third tumor line were completely different from normal. This clearly shows the heterogeneity in cancers of similar origin.
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PMID:Temperature effects on the modulation of adenylate cyclases from rat liver and Morris hepatomas. 20 95


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