title: The transcriptome that mediates increased cyclic adenosine monophosphate signaling in PRKAR1A defects and other settings.
abstract: OBJECTIVE
  To review current knowledge on the involvement of cyclic adenosine monophosphate (cAMP) and interacting signaling pathways in predisposition to tumor formation in primary pigmented nodular adrenocortical disease (PPNAD), a type of bilateral adrenal hyperplasia (BAH) related to the multiple endocrine neoplasia Carney complex, and also in isolated PPNAD and other BAHs.
  
  
  METHODS
  We review the pertinent literature and discuss genetic defects associated with various endocrine and nonendocrine tumors.
  
  
  RESULTS
  A decade ago, we discovered that PPNAD and the Carney complex are caused by PRKAR1A mutations. PRKAR1A encodes the protein kinase A (PKA) regulatory subunit type IA, an important regulator of cAMP signaling in most cells. Recently, we described PKA or PRKAR1A abnormalities in a variety of other BAHs; in some of these cases, mutations in additional genes of the cAMP signaling pathway, the phosphodiesterases, were identified. Transcriptomic analyses of human lesions or animal models showed that abnormal cAMP/PKA signaling in the adrenal glands, and also in other tissues such as bone, leads to proliferation of tissue-specific pluripotential cells through activation of Wnt signaling.
  
  
  CONCLUSIONS
  Recent findings indicate the relevance of cAMP signaling in the pathogenesis of adrenocortical disease and point to the Wnt signaling pathway as a potential important mediator of tumorigenesis related to increased cAMP or PKA signaling (or both).
authors: Section on Endocrinology and Genetics, Program on Developmental Endocrinology & Genetics, National Institutes of Health, 10 Center Drive, Bethesda, MD 20892, USA.
authors: Monalisa F
authors: MF
authors: Azevedo
authors: Constantine A
authors: CA
authors: Stratakis
mesh_terms: D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism*; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000378:metabolism*; D006801:Humans; D008954:Models, Biological; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D059467:Transcriptome / Q000235:genetics / Q000502:physiology
chemical_list: D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; D000242:Cyclic AMP