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Review
. 2011 Jul-Aug;17 Suppl 3(0 3):2-7.
doi: 10.4158/EP10412.RA.

The transcriptome that mediates increased cyclic adenosine monophosphate signaling in PRKAR1A defects and other settings

Monalisa F Azevedo  1 , Constantine A Stratakis
Affiliations
Review

The transcriptome that mediates increased cyclic adenosine monophosphate signaling in PRKAR1A defects and other settings

Monalisa F Azevedo et al. Endocr Pract. 2011 Jul-Aug.

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.

Conclusion: 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).

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Figures

Figure 1
Figure 1
The cyclic adenosine monophosphate (cAMP) signaling pathway and its genetic defects causing endocrine diseases. ATP = adeno-sine triphosphate; C = catalytic subunit of PKA; CNC = Carney complex; GDP = guanosine diphosphate; GTP = guanosine triphosphate; MAS = McCune-Albright syndrome; PDE = phosphodiesterase; PKA = protein kinase A; R = regulatory subunit of PKA; a, b, g = subunits of G protein.
See this image and copyright information in PMC

References

    1. Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore) 1985;64:270–283. - PubMed
    1. Stratakis CA, Kirschner LS, Carney JA. Clinical and molecular features of the Carney complex: diagnostic criteria and recommendations for patient evaluation. J Clin Endocrinol Metab. 2001;86:4041–4046. - PubMed
    1. Kirschner LS, Carney JA, Pack SD, et al. Mutations of the gene encoding the protein kinase A type I-alpha regulatory subunit in patients with the Carney complex. Nat Genet. 2000;26:89–92. - PubMed
    1. Marx SJ. Molecular genetics of multiple endocrine neoplasia types 1 and 2 [published correction appears in Nat Rev Cancer. 2005;5:663]. Nat Rev Cancer. 2005;5:367–375. - PubMed
    1. Bertherat J, Horvath A, Groussin L, et al. Mutations in regulatory subunit type 1A of cyclic adenosine 5′-monophosphate-dependent protein kinase (PRKAR1A): phenotype analysis in 353 patients and 80 different genotypes. J Clin Endocrinol Metab. 2009;94:2085–2091. - PMC - PubMed

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