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The phenotypic transformation of well-differentiated epithelial carcinoma into a mesenchymal-like state provides cancer cells with the ability to disseminate locally and to metastasise. Different degrees of epithelial–mesenchymal transition (EMT) have been found to occur in carcinomas from breast, colon and ovarian carcinoma (OC), among others. Numerous(More)
To understand the regulation of A2a adenosine receptor (A2a-R) response, we examined the molecular mechanisms underlying the desensitization of A2a response in rat pheochromocytoma PC12 cells, which possess an A2a-R identical with the A2a receptor we recently cloned from rat brain. Prolonged exposure of PC12 cells to adenosine agonists significantly(More)
We have previously reported that phosphorylation of adenylyl cyclase type VI (AC6) may result in the suppression of adenylyl cyclase activity during desensitization of the A2a-adenosine receptor-mediated cAMP response (A2a desensitization) in rat pheochromocytoma PC12 cells. In the present study, we demonstrate that protein kinase C (PKC) is responsible for(More)
To understand the molecular basis for the regulation of rat A2a adenosine receptor (A2a-R) expression, we have characterized the rat A2a-R gene and defined its promoter regions. Through a combination of restriction mapping and sequence analysis, we have demonstrated that the rat A2a-R gene is composed of two exons interrupted by a 7.2-kb intron. Primer(More)
Previous results from our laboratory have shown that phosphorylation of type VI adenylyl cyclase (ACVI) by protein kinase C (PKC) caused suppression of adenylyl cyclase activity. In the present study, we investigated the role of the N terminus cytosolic domain of ACVI in this PKC-mediated inhibition of ACVI. Removal of amino acids 1 to 86 of ACVI or(More)
We have isolated an adenosine receptor gene (RA2) from a rat brain cDNA library. This novel rat adenosine receptor has 410 amino acids, as deduced from its base sequence, and shows 82% amino acid identity with the dog A2 receptor. Amino acid sequence analysis indicates that RA2 protein contains seven transmembrane domains and belongs to the G(More)
The aim of this study was to investigate the distribution of a calcium-inhibitable adenylyl cyclase type VI (type VI AC) in the central nervous system using an antiserum directed against the N-terminus of type VI AC. Our results indicate that type VI AC immunoreactivity is generally expressed in many brain regions with different levels of intensity. Most(More)
The rat A2A adenosine receptor (A2A-R) gene contains two promoters, P1 and P2, which produce transcript 1 and transcript 2, respectively. These transcripts differ in the lengths of their 5' untranslated regions (5'UTR1: 514 bp, initiated from P1; 5'UTR2: 221 bp, initiated from P2) but encode the same protein. In the present study, we demonstrate that(More)
We reported earlier that inhibition of adenylyl cyclase activity is a mechanism involved in desensitization of the A2a adenosine receptor-mediated cAMP response (A2a desensitization) in rat pheochromocytoma PC-12 cells. Here, we investigated the molecular mechanism that modulates adenylyl cyclase activity during A2a desensitization. Reversible inhibition of(More)
Prolonged activation of an A2A adenosine receptor significantly inhibits the cellular response to subsequent stimulation (A2A desensitization). We have reported previously that activation of phosphodiesterase (PDE) contributes to A2A desensitization in PC12 cells. In the present study, we show that a type IV PDE (PDE4)-selective inhibitor (Ro 20-1724)(More)