ArticleMolecular endocrinology (Baltimore, Md.)2008
Mutation of Prkar1a causes osteoblast neoplasia driven by dysregulation of protein kinase A.
Article in Molecular endocrinology (Baltimore, Md.), 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 34 citations in OpenAlex.
- In vivo and in vitro analysis of functional effects of the SDHD H50R variant.Endocrine-related cancer · 2025Article
- Opportunities and Challenges of Kava in Lung Cancer Prevention.International journal of molecular sciences · 2023Review
- Suppressing the activation of protein kinase A as a DNA damage-independent mechanistic lead for dihydromethysticin prophylaxis of NNK-induced lung carcinogenesis.Carcinogenesis · 2022Article
- Review
- Bone tissue and mineral metabolism in hereditary endocrine tumors: clinical manifestations and genetic bases.Orphanet journal of rare diseases · 2020Review
- 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
- PRKAR1A is a functional tumor suppressor inhibiting ERK/Snail/E-cadherin pathway in lung adenocarcinoma.Scientific reports · 2016Article
- Osteochondromyxoma: Review of a rare carney complex criterion.Journal of bone oncology · 2016Review
- Haploinsufficiency for either one of the type-II regulatory subunits of protein kinase A improves the bone phenotype of Prkar1a+/- mice.Human molecular genetics · 2015Article
- PKA signaling drives mammary tumorigenesis through Src.Oncogene · 2015Article
- Knockdown of PRKAR1A, the gene responsible for Carney complex, interferes with differentiation in osteoblastic cells.Molecular endocrinology (Baltimore, Md.) · 2014Article
- Protein kinase A activation enhances β-catenin transcriptional activity through nuclear localization to PML bodies.PloS one · 2014Article
- cAMP/PKA signaling defects in tumors: genetics and tissue-specific pluripotential cell-derived lesions in human and mouse.Molecular and cellular endocrinology · 2013Review
- How does cAMP/protein kinase A signaling lead to tumors in the adrenal cortex and other tissues?Molecular and cellular endocrinology · 2011Review
- Protein kinase A regulates caspase-1 via Ets-1 in bone stromal cell-derived lesions: a link between cyclic AMP and pro-inflammatory pathways in osteoblast progenitors.Human molecular genetics · 2011Article
- PRKAR1A and the evolution of pituitary tumors.Molecular and cellular endocrinology · 2010Review
- Prkar1a is an osteosarcoma tumor suppressor that defines a molecular subclass in mice.The Journal of clinical investigation · 2010Article
- Neural crest-specific loss of Prkar1a causes perinatal lethality resulting from defects in intramembranous ossification.Molecular endocrinology (Baltimore, Md.) · 2010Article
- Alternate protein kinase A activity identifies a unique population of stromal cells in adult bone.Proceedings of the National Academy of Sciences of the United States of America · 2010Article
- Cyclic nucleotide signaling in polycystic kidney disease.Kidney international · 2010Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Carney complex (CNC) is an autosomal dominant neoplasia syndrome caused by inactivating mutations in PRKAR1A, the gene encoding the type 1A regulatory subunit of protein kinase A (PKA). This genetic defect induces skin pigmentation, endocrine tumors, myxomas, and schwannomas. Some patients with the complex also develop myxoid bone tumors termed osteochondromyxomas. To study the link between the PRKAR1A mutations and tumor formation, we generated a mouse model of this condition. Prkar1a(+/-) mice develop bone tumors with high frequency, although these lesions have not yet been characterized, either from human patients or from mice. Bone tumors from Prkar1a(+/-) mice were heterogeneous, including elements of myxomatous, cartilaginous, and bony differentiation that effaced the normal bone architecture. Immunohistochemical analysis identified an osteoblastic origin for the abnormal cells associated with islands of bone. To better understand these cells at the biochemical level, we isolated primary cultures of tumoral bone and compared them with cultures of bone from wild-type animals. The tumor cells exhibited the expected decrease in Prkar1a protein and exhibited increased PKA activity. At the phenotypic level, we observed that tumor cells behaved as incompletely differentiated osteoblasts and were able to form tumors in immunocompromised mice. Examination of gene expression revealed down-regulation of markers of bone differentiation and increased expression of locally acting growth factors, including members of the Wnt signaling pathway. Tumor cells exhibited enhanced growth in response to PKA-stimulating agents, suggesting that tumorigenesis in osteoblast precursor cells is driven by effects directly mediated by the dysregulation of PKA.
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