Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0043167 (pertussis)
 19,595 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Calcitonin may induce cyclic AMP production by breast cancer cells and inhibit their growth. The molecular complex leading to cyclic AMP production in response to calcitonin is made of the calcitonin receptor coupled to the adenylate cyclase by at least one guanine nucleotide-binding protein (G-protein, of the Gs type). Our aim was to determine whether and how the responses of cells to calcitonin were modulated by growth-regulating agents not directly acting through the cyclic AMP pathway. We found that the cyclic AMP response to calcitonin was reduced after preincubation of cells with the mitogens 17beta-estradiol and epidermal growth factor (EGF), while it was enhanced after preincubation with the growth inhibitors tamoxifen and 1,25(OH)2D3, as well as with an antisense oligonucleotide to the proto-oncogene c-myc. Scatchard-plots revealed no significant change in the calcitonin receptor number or affinity. On the other hand, the cyclic AMP production of cells in response to activators unrelated to calcitonin, such as forskolin, a direct adenylate cyclase effector, and isoproterenol, a beta-adrenergic receptor agonist, was modulated only weakly or not at all by the growth-regulating agents. This suggested that the effects observed were essentially calcitonin-specific and associated with events located between the calcitonin receptor and the adenylate cyclase. Since a Go- or Gi-protein has been previously implicated in the calcitonin signal transduction, we tested the action of pertussis toxin, a specific inhibitor of these G-proteins. Pertussis toxin produced a general increase in the cyclic AMP response of cells to calcitonin; moreover, the toxin almost abolished the effect of mitogens and antimitogens on that parameter. We conclude that in breast cancer cells, the calcitonin receptor and the adenylate cyclase are coupled by at least one Go/Gi-protein sensitive to growth-regulating agents; this results in a modulation of the cyclic AMP response to calcitonin by these agents. On the other hand, the growth-inhibitory effect of calcitonin on breast cancer cells was reduced by 17beta-estradiol and enhanced by tamoxifen. We suggest that this could be a consequence of changes in cyclic AMP levels and deserves further investigation.
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PMID:Breast cancer cell response to calcitonin: modulation by growth-regulating agents. 960 Jun 64

In C9 (Clone 9) liver cells, angiotensin 11 increased the intracellular Ca2+ content, inositol phosphate production and c-fos mRNA expression. Other angiotensins were also active with the order of potency being angiotensin II = angiotensin III >> angiotensin I > angiotensin IV. Losartan, but not PD 123177 (1-(4-amino-3-methyl)-5-diphenylacetyl-4,5,6,7-tetrahydro-1H-imida zo [4,5c]pyridine-6-carboxylic acid), blocked the effects of angiotensin II. Pertussis toxin did not alter these actions of angiotensin II. These data indicate that the effects were mediated through angiotensin AT1 receptors involving pertussis toxin-insensitive G-proteins. Phorbol myristate acetate was also able to increase c-fos mRNA expression. The action of angiotensin II was consistently greater than that of the active phorbol ester. Staurosporine but not genistein inhibited this effect of angiotensin II. Angiotensin II- and phorbol myristate acetate-induced proto-oncogene mRNA expression was attenuated in cells incubated overnight with the active phorbol ester, which suggests a major role of protein kinase C.
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PMID:Angiotensin AT1 receptors in Clone 9 rat liver cells: Ca2+ signaling and c-fos expression. 987 76

A growing body of evidence concerning estrogen effects cannot be explained by the classic model of hormone action, which involves the binding to estrogen receptors (ERs) alpha and ERbeta and the interaction of the steroid-receptor complex with specific DNA sequences associated with target genes. Using c-fos proto-oncogene expression as an early molecular sensor of estrogen action in ERalpha-positive MCF7 and ER-negative SKBR3 breast cancer cells, we have discovered that 17beta-estradiol (E2), and the two major phytoestrogens, genistein and quercetin, stimulate c-fos expression through ERalpha as well as through an ER-independent manner via the G protein-coupled receptor homologue GPR30. The c-fos response is repressed in GPR30-expressing SKBR3 cells transfected with an antisense oligonucleotide against GPR30 and reconstituted in GPR30-deficient MDA-MB 231 and BT-20 breast cancer cells transfected with a GPR30 expression vector. GPR30-dependent activation of ERK1/2 by E2 and phytoestrogens occurs via a Gbetagamma-associated pertussis toxin-sensitive pathway that requires both Src-related and EGF receptor tyrosine kinase activities. The ability of E2 and phytoestrogens to regulate the expression of growth-related genes such as c-fos even in the absence of ER has interesting implications for understanding breast cancer progression.
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PMID:The G protein-coupled receptor GPR30 mediates c-fos up-regulation by 17beta-estradiol and phytoestrogens in breast cancer cells. 1509 May 35


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