Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:4.6.1.1 (adenylate cyclase)
 19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We investigated the role of three different signal transduction systems adenylate-cyclase (AC), protein kinase C (PKC) and tyrosine kinase (TK) for growth and invasion of a human follicular (FTC133) and a human papillary thyroid cancer cell line (PTC-UC1). Cyclic AMP stimulators and inhibitors had no effect at any concentration. The PKC agonist TPA enhanced both growth and invasion of FTC133 by 15%, whereas staurosporine, a PKC antagonist, inhibited growth by 47% and invasion by 32%. The latter also reversed thyrotropin (TSH) stimulation, but not epidermal growth factor (EFG) stimulation. EGF-stimulated growth and invasion of both cell lines were abolished by EGF-receptor antagonism using a monoclonal antibody. The tyrosine kinase antagonist genistein reversed EGF, but not TSH, stimulation. Pertussis toxin inhibited growth (FTC133: 22%) and invasion (FTC133: 18%). Cholera toxin was less inhibitory. Obviously, signal transduction of differentiated thyroid cancer is complex and systems other than adenylate cyclase are crucial for basal invasion and growth of follicular thyroid cancer cells in culture.
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PMID:[Growth and invasion of differentiated thyroid gland carcinoma: importance of signal transduction]. 776 Jun 57

After collagenase digestion and Percoll density gradient centrifugation of human renal tissue, tubular epithelial cells of the proximal and the distal segments were isolated with an immunomagnetic method using MACS microbeads. To enrich proximal tubular (PT) cells we used a monoclonal antibody (mAb) against aminopeptidase M (APM, CD 13), specific of the proximal tubule. Distal tubular (DT) cells were isolated through a mAb recognizing Tamm-Horsfall glycoprotein (THG), a specific antigen for the thick ascending limb and the early distal convoluted tubule. Cells of the proximal primary isolate were histochemically strongly positive for aminopeptidase M (98.6%), however, cells of the distal portion were negative (98.7%). Ultrastructural analysis of PTC primary isolates revealed highly preserved brush border microvilli, well-developed endocytosis apparati and numerous mitochondria, whereas DTC primary isolates showed smaller cells with basolateral invaginations and less apical microvilli. Characterization by immunofluorescence indicated the coexpression of cytokeratin and vimentin, whereas staining for desmin, smooth muscle actin, a fibroblast-specific marker and von Willebrand factor was negative. Cultured PT and DT cells displayed different adenylate cyclase responsiveness to hormonal stimulation. PTH (10(-6) M) increased cAMP production in distal cells up to 32.8-fold of the basal level and in proximal only up to 3.5-fold (10(-8) M, DT 14.4x and PT 2.25x). Calcitonin stimulated adenylate cyclase in DT in a dose dependent fashion (10(-6) M, 4.3x; 10(-8) M, 2.25x), whereas only a low calcitonin response was found in PT cells (10(-6) M, 1.6x; 10(-8) M, 1.4x). AVP (10(-6) M) activated the distal cAMP-production only up to 1.9x of the basal level, but the proximal cAMP-production was negligible (only 1.3x the basal level). The data of this study indicate the proximal and distal tubule origin of the cultured cells that were isolated according to their segment-specific antigens.
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PMID:Isolation of proximal and distal tubule cells from human kidney by immunomagnetic separation. Technical note. 935 Jun 55

The main regulating systems of thyroid growth are the mitogen-activated protein kinase (MAPK) signaling pathway and the cAMP signaling pathway. Thyroid papillary carcinoma frequently involves mutations in BRAF or RET/PTC without overlap, which are expected to constitutively activate MAPK signaling. On the other hand, it has been reported that cAMP signaling acts in an inhibitory manner on the proliferation of papillary carcinoma cell lines, although the cAMP pathway physiologically promotes the proliferation of normal follicular cells as well as hormonogenesis. The effect of cAMP on proliferation is attributed to crosstalk with MAPK signaling. However, this phenomenon has not been clearly established in papillary carcinoma with BRAF or RET/PTC mutations. In order to elucidate whether activated cAMP signaling inhibits cell proliferation and affects MAPK signaling in papillary carcinoma, we performed in vitro experiments using two representative cell lines, K1 and TPC-1, which have a BRAF and an RET/PTC mutation, respectively. Elevated cAMP caused by an adenylate cyclase activator suppressed the proliferation of both K1 and TPC-1 cells. Examining the crosstalk between cAMP and MAPK signaling, K1 and TPC-1 cells showed opposite responses to cAMP activation. These responses were blocked by an inhibitor of the cAMP-dependent protein kinase (PKA). In K1 cells, B-Raf might predominate over Raf-1, and the elevated cAMP is thought to promote MAPK phosphorylation through the PKA-mediated activation of Rap1. On the other hand, in TPC-1 cells Raf-1 might predominate and could be inhibited by activated Rap1, resulting in the suppression of MAPK phosphorylation. In conclusion, the proliferation of both papillary carcinoma cell types was significantly suppressed by cAMP signaling, regardless of whether MAPK signaling was activated or inactivated by the PKA-mediated cAMP signaling pathway. There could, however, be other mechanisms by which cAMP signaling inhibits the growth of papillary carcinoma cells.
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PMID:Cyclic AMP-mediated growth suppression and MAPK phosphorylation in thyroid papillary carcinoma cells. 2147 4