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http://purl.uniprot.org/citations/17904549http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/17904549http://www.w3.org/2000/01/rdf-schema#comment"The four regulatory subunits (R1A, R1B, R2A, R2B) of protein kinase A (PKA) are differentially expressed in several cancer cell lines and exert distinct roles in growth control. Mutations of the R1A gene have been found in patients with Carney complex and in a minority of sporadic primary pigmented nodular adrenocortical disease (PPNAD). The aim of this study was to evaluate the expression of PKA regulatory subunits in non-PPNAD adrenocortical tumors causing ACTH-independent Cushing's syndrome and to test the impact of differential expression of these subunits on cell growth. Immunohistochemistry demonstrated a defective expression of R2B in all cortisol-secreting adenomas (n=16) compared with the normal counterpart, while both R1A and R2A were expressed at high levels in the same tissues. Conversely, carcinomas (n=5) showed high levels of all subunits. Sequencing of R1A and R2B genes revealed a wild type sequence in all tissues. The effect of R1/R2 ratio on proliferation was assessed in mouse adrenocortical Y-1 cells. The R2-selective cAMP analogue 8-Cl-cAMP dose-dependently inhibited Y-1 cell proliferation and induced apoptosis, while the R1-selective cAMP analogue 8-HA-cAMP stimulated cell proliferation. Finally, R2B gene silencing induced up-regulation of R1A protein, associated with an increase in cell proliferation. In conclusion, we propose that a high R1/R2 ratio favors the proliferation of well differentiated and hormone producing adrenocortical cells, while unbalanced expression of these subunits is not required for malignant transformation."xsd:string
http://purl.uniprot.org/citations/17904549http://purl.org/dc/terms/identifier"doi:10.1016/j.yexcr.2007.08.024"xsd:string
http://purl.uniprot.org/citations/17904549http://purl.uniprot.org/core/author"Ferrero S."xsd:string
http://purl.uniprot.org/citations/17904549http://purl.uniprot.org/core/author"Spada A."xsd:string
http://purl.uniprot.org/citations/17904549http://purl.uniprot.org/core/author"Arnaldi G."xsd:string
http://purl.uniprot.org/citations/17904549http://purl.uniprot.org/core/author"Beck-Peccoz P."xsd:string
http://purl.uniprot.org/citations/17904549http://purl.uniprot.org/core/author"Bondioni S."xsd:string
http://purl.uniprot.org/citations/17904549http://purl.uniprot.org/core/author"Pellegrini C."xsd:string
http://purl.uniprot.org/citations/17904549http://purl.uniprot.org/core/author"Mantovani G."xsd:string
http://purl.uniprot.org/citations/17904549http://purl.uniprot.org/core/author"Bosari S."xsd:string
http://purl.uniprot.org/citations/17904549http://purl.uniprot.org/core/author"Vicentini L."xsd:string
http://purl.uniprot.org/citations/17904549http://purl.uniprot.org/core/author"Lania A.G."xsd:string
http://purl.uniprot.org/citations/17904549http://purl.uniprot.org/core/author"Pedroni C."xsd:string
http://purl.uniprot.org/citations/17904549http://purl.uniprot.org/core/author"Peverelli E."xsd:string
http://purl.uniprot.org/citations/17904549http://purl.uniprot.org/core/date"2008"xsd:gYear
http://purl.uniprot.org/citations/17904549http://purl.uniprot.org/core/name"Exp Cell Res"xsd:string
http://purl.uniprot.org/citations/17904549http://purl.uniprot.org/core/pages"123-130"xsd:string
http://purl.uniprot.org/citations/17904549http://purl.uniprot.org/core/title"Different expression of protein kinase A (PKA) regulatory subunits in cortisol-secreting adrenocortical tumors: relationship with cell proliferation."xsd:string
http://purl.uniprot.org/citations/17904549http://purl.uniprot.org/core/volume"314"xsd:string
http://purl.uniprot.org/citations/17904549http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/17904549
http://purl.uniprot.org/citations/17904549http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/17904549
http://purl.uniprot.org/uniprot/#_A3R6R8-mappedCitation-17904549http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17904549
http://purl.uniprot.org/uniprot/#_A1XGZ0-mappedCitation-17904549http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17904549
http://purl.uniprot.org/uniprot/#_B2R5T5-mappedCitation-17904549http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/17904549