ArticleThe Journal of clinical endocrinology and metabolism2012
Activation of cyclic AMP signaling leads to different pathway alterations in lesions of the adrenal cortex caused by germline PRKAR1A defects versus those due to somatic GNAS mutations.
Article in The Journal of clinical endocrinology and metabolism, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 68 citations in OpenAlex.
- Review
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- Primary bilateral macronodular adrenal hyperplasia: definitely a genetic disease.Nature reviews. Endocrinology · 2022Review
- An Overview of the Heterogeneous Causes of Cushing Syndrome Resulting From Primary Macronodular Adrenal Hyperplasia (PMAH).Journal of the Endocrine Society · 2022Review
- Genetic Alterations in Benign Adrenal Tumors.Biomedicines · 2022Review
- Disorders of the adrenal cortex: Genetic and molecular aspects.Frontiers in endocrinology · 2022Review
- Bilateral Adrenal Hyperplasia: Pathogenesis and Treatment.Biomedicines · 2021Review
- GPharmacological reviews · 2021Review
- ARMC5 variants in PRKAR1A-mutated patients modify cortisol levels and Cushing's syndrome.Endocrine-related cancer · 2020Article
- Molecular Basis of Primary Aldosteronism and Adrenal Cushing Syndrome.Journal of the Endocrine Society · 2020Review
- High expression of adrenal P450 aromatase (CYP19A1) in association with ARMC5-primary bilateral macronodular adrenocortical hyperplasia.The Journal of steroid biochemistry and molecular biology · 2019Article
- DNA Methylation Profiling Reveals Prognostically Significant Groups in Pediatric Adrenocortical Tumors: A Report From the International Pediatric Adrenocortical Tumor Registry.JCO precision oncology · 2019Article
- Genetics of Adrenocortical Development and Tumors.Endocrinology and metabolism clinics of North America · 2017Review
- Cell signaling pathways in the adrenal cortex: Links to stem/progenitor biology and neoplasia.Molecular and cellular endocrinology · 2017Review
- Celecoxib treatment of fibrous dysplasia (FD) in a human FD cell line and FD-like lesions in mice with protein kinase A (PKA) defects.Molecular and cellular endocrinology · 2017Article
- Persistent Diabetes Mellitus Postadrenalectomy in Neonatal McCune-Albright Syndrome.Global pediatric health · 2017Article
- PKA inhibits WNT signalling in adrenal cortex zonation and prevents malignant tumour development.Nature communications · 2016Article
- A genetic and molecular update on adrenocortical causes of Cushing syndrome.Nature reviews. Endocrinology · 2016Review
- The Role of gsp Mutations on the Development of Adrenocortical Tumors and Adrenal Hyperplasia.Frontiers in endocrinology · 2016Review
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 2 countries.
Funding
Abstract
contextThe overwhelming majority of benign lesions of the adrenal cortex leading to Cushing syndrome are linked to one or another abnormality of the cAMP or protein kinase pathway. PRKAR1A-inactivating mutations are responsible for primary pigmented nodular adrenocortical disease, whereas somatic GNAS activating mutations cause macronodular disease in the context of McCune-Albright syndrome, ACTH-independent macronodular hyperplasia, and, rarely, cortisol-producing adenomas. OBJECTIVE AND
designThe whole-genome expression profile (WGEP) of normal (pooled) adrenals, PRKAR1A- (3) and GNAS-mutant (3) was studied. Quantitative RT-PCR and Western blot were used to validate WGEP findings.
resultsMAPK and p53 signaling pathways were highly overexpressed in all lesions against normal tissue. GNAS-mutant tissues were significantly enriched for extracellular matrix receptor interaction and focal adhesion pathways when compared with PRKAR1A-mutant (fold enrichment 3.5, P < 0.0001 and 2.1, P < 0.002, respectively). NFKB, NFKBIA, and TNFRSF1A were higher in GNAS-mutant tumors (P < 0.05). Genes related to the Wnt signaling pathway (CCND1, CTNNB1, LEF1, LRP5, WISP1, and WNT3) were overexpressed in PRKAR1A-mutant lesions.
conclusionWGEP analysis revealed that not all cAMP activation is the same: adrenal lesions harboring PRKAR1A or GNAS mutations share the downstream activation of certain oncogenic signals (such as MAPK and some cell cycle genes) but differ substantially in their effects on others.
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