title: PRKAR1A and the evolution of pituitary tumors.
abstract: Carney complex (CNC) is an inherited tumor predisposition associated with pituitary tumors, including GH-producing pituitary adenomas and rare reports of prolactinomas. This disease is caused by mutations in PRKAR1A, which encodes the type 1A regulatory subunit of the cAMP-dependent protein kinase, PKA. Loss of PRKAR1A causes enhanced PKA signaling, which leads to pituitary tumorigenesis. Mutations in the gene have not been detected in sporadic pituitary tumors, but there is some data to suggest that non-genomic mechanisms may cause loss of protein expression. Unlike CNC patients, mice heterozygous for Prkar1a mutations do not develop pituitary tumors, although complete knockout of the gene in the Pit1 lineage of the pituitary produces GH-secreting pituitary adenomas. These data indicate that complete loss of Prkar1a/PRKAR1A is able to cause pituitary tumors in mice and men. The pattern of tumors is likely related to the signaling pathways employed in specific pituitary cell types.
authors.affiliation: Division of Endocrinology, Diabetes and Metabolism, Department of Internal Medicine, The Ohio State University, Columbus, OH 43210, USA. Lawrence.Kirschner@osumc.edu
authors.forename: Lawrence S
authors.initials: LS
authors.lastname: Kirschner
mesh_terms: D000172:Acromegaly / Q000209:etiology; D000818:Animals; D056733:Carney Complex / Q000235:genetics*; D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / Q000235:genetics*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D049912:Growth Hormone-Secreting Pituitary Adenoma / Q000473:pathology; D006801:Humans; D051379:Mice; D009232:Myxoma / Q000209:etiology / Q000401:mortality; D010902:Pituitary Gland / Q000378:metabolism / Q000473:pathology; D010911:Pituitary Neoplasms / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D015175:Prolactinoma / Q000378:metabolism / Q000473:pathology; D052683:Somatotrophs / Q000473:pathology
chemical_list: D054756:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; C517834:PRKAR1A protein, human; C517835:Prkar1a protein, mouse; D017868:Cyclic AMP-Dependent Protein Kinases
references.citation: Nat Genet. 2006 Jul;38(7):794-800
references.pmid: 16767104
references.citation: Cancer Res. 2004 Dec 15;64(24):8811-5
references.pmid: 15604237
references.citation: Hum Mol Genet. 2010 Apr 15;19(8):1387-98
references.pmid: 20080939
references.citation: Clin Endocrinol (Oxf). 2003 Apr;58(4):464-70
references.pmid: 12641630
references.citation: Genomics. 1999 Nov 15;62(1):21-33
references.pmid: 10585764
references.citation: J Neurosurg. 2000 Mar;92(3):413-8
references.pmid: 10701527
references.citation: J Clin Endocrinol Metab. 2009 Jun;94(6):2085-91
references.pmid: 19293268
references.citation: Circulation. 2008 Mar 18;117(11):1414-22
references.pmid: 18316483
references.citation: Endocrinology. 2001 Sep;142(9):3764-73
references.pmid: 11517152
references.citation: Horm Res. 2009;71(3):132-41
references.pmid: 19188737
references.citation: Cancer Res. 2005 Nov 15;65(22):10307-15
references.pmid: 16288019
references.citation: J Med Genet. 2002 Dec;39(12):e78
references.pmid: 12471216
references.citation: Orphanet J Rare Dis. 2006 Jun 06;1:21
references.pmid: 16756677
references.citation: J Clin Invest. 1996 Feb 1;97(3):699-705
references.pmid: 8609225
references.citation: Curr Opin Oncol. 2007 Jan;19(1):24-9
references.pmid: 17133108
references.citation: Endocrinology. 2009 Jul;150(7):3177-85
references.pmid: 19342460
references.citation: Science. 2006 May 26;312(5777):1228-30
references.pmid: 16728643
references.citation: J Med Genet. 2004 Aug;41(8):596-600
references.pmid: 15286154
references.citation: Proc Natl Acad Sci U S A. 2005 Jun 28;102(26):9218-23
references.pmid: 15972329
references.citation: Endocr Rev. 2001 Oct;22(5):675-705
references.pmid: 11588148
references.citation: J Pediatr Endocrinol Metab. 2000 Apr;13(4):373-9
references.pmid: 10776991
references.citation: Mol Endocrinol. 2008 Feb;22(2):380-7
references.pmid: 17975024
references.citation: J Clin Endocrinol Metab. 2005 Dec;90(12):6721-4
references.pmid: 16204369
references.citation: Genes Chromosomes Cancer. 2005 May;43(1):72-82
references.pmid: 15704128
references.citation: Br J Dermatol. 1997 Apr;136(4):578-82
references.pmid: 9155962
references.citation: Nature. 1991 Mar 7;350(6313):74-7
references.pmid: 1848356
references.citation: Hum Mol Genet. 2000 Dec 12;9(20):3037-46
references.pmid: 11115848
references.citation: Eur J Hum Genet. 2008 Oct;16(10):1245-53
references.pmid: 18431404
references.citation: J Biol Chem. 2007 Dec 7;282(49):35924-32
references.pmid: 17916558
references.citation: Cancer Res. 2004 Dec 15;64(24):9193-8
references.pmid: 15604292
references.citation: Recent Prog Horm Res. 1995;50:35-73
references.pmid: 7740167
references.citation: Cancer Res. 2005 Jun 1;65(11):4506-14
references.pmid: 15930266
references.citation: Proc Natl Acad Sci U S A. 2004 Sep 28;101(39):14222-7
references.pmid: 15371594
references.citation: Semin Dermatol. 1995 Jun;14(2):90-8
references.pmid: 7640202
references.citation: Methods Mol Biol. 2000;136:477-85
references.pmid: 10840735
references.citation: Genesis. 2008 Jan;46(1):37-42
references.pmid: 18196598
references.citation: Oncogene. 2000 Apr 6;19(15):1875-84
references.pmid: 10773877
references.citation: Clin Endocrinol (Oxf). 2002 Oct;57(4):443-8
references.pmid: 12354125
references.citation: Mol Endocrinol. 2008 Feb;22(2):430-40
references.pmid: 17932105
references.citation: J Mol Endocrinol. 2003 Apr;30(2):87-97
references.pmid: 12683933
references.citation: Endocr Relat Cancer. 2009 Sep;16(3):773-93
references.pmid: 19470615
references.citation: Endocr Rev. 2001 Dec;22(6):724-63
references.pmid: 11739329
references.citation: J Clin Endocrinol Metab. 2001 Sep;86(9):4041-6
references.pmid: 11549623
references.citation: J Biol Chem. 2002 Jul 26;277(30):27294-304
references.pmid: 12004056
references.citation: Lancet Oncol. 2005 Jul;6(7):501-8
references.pmid: 15992699
references.citation: Nat Genet. 2000 Sep;26(1):89-92
references.pmid: 10973256
references.citation: J Clin Endocrinol Metab. 2000 Oct;85(10):3860-5
references.pmid: 11061550
references.citation: Medicine (Baltimore). 1985 Jul;64(4):270-83
references.pmid: 4010501
references.citation: Endocrinology. 1995 Sep;136(9):4147-50
references.pmid: 7649123
references.citation: Pituitary. 2004;7(2):73-82
references.pmid: 15761655