Clinical and molecular genetics of acromegaly: MEN1, Carney complex, McCune-Albright syndrome, familial acromegaly and genetic defects in sporadic tumors

Reviews in Endocrine and Metabolic Disorders

Volumn 9, Issue 1, 2008, Pages 1-11

  Horvath, Anelia ^a   Stratakis, Constantine A ^a  

^a EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH AND HUMAN DEVELOPMENT   (United States)

Author keywords

Carney complex; Growth factors; Multiple endocrine neoplasia; Oncogenes; Pituitary tumors; Tumor suppressor genes

Indexed keywords

GROWTH HORMONE;

ACROMEGALY; ALBRIGHT SYNDROME; CANCER PATIENT; CARCINOGENESIS; CARNEY COMPLEX; CLINICAL FEATURE; CONGENITAL BLINDNESS; DIAGNOSTIC IMAGING; GENE MUTATION; GENETIC DISORDER; HUMAN; HYPOPHYSIS TUMOR; MOLECULAR GENETICS; NONHUMAN; REVIEW;

ACROMEGALY; ADENOMA; ANIMALS; DISEASE MODELS, ANIMAL; FIBROUS DYSPLASIA, POLYOSTOTIC; HUMANS; MULTIPLE ENDOCRINE NEOPLASIA TYPE 1; PITUITARY NEOPLASMS;

EID: 39149135836     PISSN: 13899155     EISSN: None     Source Type: Journal    
DOI: 10.1007/s11154-007-9066-9     Document Type: Review

References (115)

1. Jagannathan J, Dumont AS, Prevedello DM, Lopes B, Oskouian RJ, Jane JA Jr, et al. Genetics of pituitary adenomas: current theories and future implications. Neurosurg Focus 2005;19(5):E4.
2. Lania A, Mantovani G, Spada A. Genetics of pituitary tumors: Focus on G-protein mutations. Exp Biol Med (Maywood) 2003;228(9):1004-17.
3. Heaney AP, Melmed S. Molecular targets in pituitary tumours. Nat Rev Cancer 2004;4(4):285-95.
4. Arafah BM, Nasrallah MP. Pituitary tumors: pathophysiology, clinical manifestations and management. Endocr Relat Cancer 2001;8(4):287-305.
5. Asa SL, Ezzat S. The pathogenesis of pituitary tumours. Nat Rev Cancer 2002;2(11):836-49.
6. Alexander JM, Biller BM, Bikkal H, Zervas NT, Arnold A, Klibanski A. Clinically nonfunctioning pituitary tumors are monoclonal in origin. J Clin Invest 1990;86(1):336-40.
7. Koch G, Tiwisina T. Beitrag zur Erblichkeit der Akromegalie und der Hyperostosis generalisata mit Pachydermie. Aerztl Forsch 1959;13:489-504.
8. Pestell RG, Alford FP, Best JD. Familial acromegaly. Acta Endocrinol (Copenh) 1989;121(2):286-9.
9. McCarthy MI, Noonan K, Wass JA, Monson JP. Familial acromegaly: studies in three families. Clin Endocrinol (Oxf) 1990;32(6):719-28.
10. Singh H, Uniyal JP, Jha P, Takker D, Murguesan K, Hingorani V, et al. Pharmacokinetics of norethindrone acetate in women after the insertion of a single subdermal implant releasing norethindrone acetate. Acta Endocrinol (Copenh) 1982;99(2):302-8.
11. Carney JA, Gordon H, Carpenter PC, Shenoy BV, Go VL. The complex of myxomas, spotty pigmentation, and endocrine overactivity. Medicine (Baltimore) 1985;64(4):270-83.
12. Akintoye SO, Chebli C, Booher S, Feuillan P, Kushner H, Leroith D, et al. Characterization of gsp-mediated growth hormone excess in the context of McCune-Albright syndrome. J Clin Endocrinol Metab 2002;87(11):5104-12.
13. Thakker RV. Multiple endocrine neoplasia-syndromes of the twentieth century. J Clin Endocrinol Metab 1998;83:2617-20.
14. Guru SC, Agarwal SK, Manickam P, Olufemi SE, Crabtree JS, Weisemann JM, et al. A transcript map for the 2.8-Mb region containing the multiple endocrine neoplasia type 1 locus. Genome Res 1997;7(7):725-35.
15. Brown MA, Solomon E. Studies on inherited cancers: outcomes and challenges of 25 years. Trends Genet 1997;13(5):202-6.
16. Larsson C, Skogseid B, Oberg K, Nakamura Y, Nordenskjold M. Multiple endocrine neoplasia type 1 gene maps to chromosome 11 and is lost in insulinoma. Nature 1988;332(6159):85-7.
17. Thakker RV, Bouloux P, Wooding C, Chotai K, Broad PM, Spurr NK, Besser GM, O'Riordan JL. Association of parathyroid tumors in multiple endocrine neoplasia type 1 with loss of alleles on chromosome 11. N Engl J Med 1989;321(4):218-24.
18. Agarwal SK, Kennedy PA, Scacheri PC, Novotny EA, Hickman AB, Cerrato A, et al. Menin molecular interactions: insights into normal functions and tumorigenesis. Horm Metab Res 2005;37(6):369-74.
19. Khodaei-O'Brien S, Zablewska B, Fromaget M, Bylund L, Weber G, Gaudray P. Heterogeneity at the 5′-end of MEN1 transcripts. Biochem Biophys Res Commun 2000;276(2):508-14.
20. Lemos MC, Thakker RV. Multiple endocrine neoplasia type 1 (MEN1): analysis of 1336 mutations reported in the first decade following identification of the gene. Hum Mutat 2007 (in press)
21. Marx SJ, Agarwal SK, Kester MB, Heppner C, Kim YS, Skarulis MC, et al. Multiple endocrine neoplasia type 1: clinical and genetic features of the hereditary endocrine neoplasias. Recent Prog Horm Res 1999;54:397-438.
22. Tsukada T, Yamaguchi K, Kameya T. The MEN1 gene and associated diseases: an update. Endocr Pathol 2001;12(3):259-73.
23. Verges B, Boureille F, Goudet P, Murat A, Beckers A, Sassolas G, et al. Pituitary disease in MEN type 1 (MEN1): data from the France-Belgium MEN1 multicenter study. J Clin Endocrinol Metab 2002;87(2):457-65.
24. Daly AF, Jaffrain-Rea ML, Beckers A. Clinical and genetic features of familial pituitary adenomas. Horm Metab Res 2005;37(6):347-54.
25. Wautot V, Vercherat C, Lespinasse J, Chambe B, Lenoir GM, Zhang CX, et al. Germline mutation profile of MEN1 in multiple endocrine neoplasia type 1: search for correlation between phenotype and the functional domains of the MEN1 protein. Hum Mutat 2002;20(1):35-47.
26. Pellegata NS, Quintanilla-Martinez L, Siggelkow H, Samson E, Bink K, Hofler H, et al. Germ-line mutations in p27Kip1 cause a multiple endocrine neoplasia syndrome in rats and humans. Proc Natl Acad Sci USA 2006;103(42):15558-63.
27. Georgitsi M, Raitila A, Karhu A, van der Luijt RB, Aalfs CM, Sane T, et al. Germline CDKN1B/p27Kip1 mutation in multiple endocrine neoplasia. J Clin Endocrinol Metab. 2007;92:3321-5.
28. Guru SC, Goldsmith PK, Burns AL, Marx SJ, Spiegel AM, Collins FS, et al. Menin, the product of the MEN1 gene, is a nuclear protein. Proc Natl Acad Sci USA 1998;95(4):1630-4.
29. Huang SC, Zhuang Z, Weil RJ, Pack S, Wang C, Krutzsch HC, et al. Nuclear/cytoplasmic localization of the multiple endocrine neoplasia type 1 gene product, menin. Lab Invest 1999;79(3):301-10.
30. La P, Desmond A, Hou Z, Silva AC, Schnepp RW, Hua X. Tumor suppressor menin: the essential role of nuclear localization signal domains in coordinating gene expression. Oncogene 2006;25(25):3537-46.
31. La P, Silva AC, Hou Z, Wang H, Schnepp RW, Yan N, et al. Direct binding of DNA by tumor suppressor menin. J Biol Chem 2004;279(47):49045-54.
32. Pfarr CM, Mechta F, Spyrou G, Lallemand D, Carillo S, Yaniv M. Mouse JunD negatively regulates fibroblast growth and antagonizes transformation by ras. Cell 1994;76(4):747-60.
33. Heppner C, Bilimoria KY, Agarwal SK, Kester M, Whitty LJ, Guru SC, et al. The tumor suppressor protein menin interacts with NF-kappaB proteins and inhibits NF-kappaB-mediated transactivation. Oncogene 2001;20(36):4917-25.
34. Kaji H, Canaff L, Lebrun JJ, Goltzman D, Hendy GN. Inactivation of menin, a Smad3-interacting protein, blocks transforming growth factor type beta signaling. Proc Natl Acad Sci USA 2001;98(7):3837-42.
35. Sowa H, Kaji H, Hendy GN, Canaff L, Komori T, Sugimoto T, et al. Menin is required for bone morphogenetic protein 2- and transforming growth factor beta-regulated osteoblastic differentiation through interaction with Smads and Runx2. J Biol Chem 2004;279(39):40267-75.
36. Lemmens IH, Forsberg L, Pannett AA, Meyen E, Piehl F, Turner JJ, et al. Menin interacts directly with the homeobox-containing protein Pem. Biochem Biophys Res Commun 2001;286(2):426-31.
37. Hughes CM, Rozenblatt-Rosen O, Milne TA, Copeland TD, Levine SS, Lee JC, et al. Menin associates with a trithorax family histone methyltransferase complex and with the hoxc8 locus. Mol Cell 2004;13(4):587-97.
38. Yokoyama A, Wang Z, Wysocka J, Sanyal M, Aufiero DJ, Kitabayashi I, et al. Leukemia proto-oncoprotein MLL forms a SET1-like histone methyltransferase complex with menin to regulate Hox gene expression. Mol Cell Biol 2004;24(13):5639-49.
39. Bai F, Pei XH, Nishikawa T, Smith MD, Xiong Y. p18Ink4c, but not p27Kip1, collaborates with Men1 to suppress neuroendocrine organ tumors. Mol Cell Biol 2007;27(4):1495-504.
40. Yoshino A, Katayama Y, Ogino A, Watanabe T, Yachi K, Ohta T, et al. Promoter hypermethylation profile of cell cycle regulator genes in pituitary adenomas. J Neurooncol 2007;83(2):153-62.
41. Sukhodolets KE, Hickman AB, Agarwal SK, Sukhodolets MV, Obungu VH, Novotny EA, et al. The 32-kilodalton subunit of replication protein A interacts with menin, the product of the MEN1 tumor suppressor gene. Mol Cell Biol 2003;23(2):493-509.
42. Jin S, Mao H, Schnepp RW, Sykes SM, Silva AC, D'Andrea AD, et al. Menin associates with FANCD2, a protein involved in repair of DNA damage. Cancer Res 2003;63(14):4204-10.
43. Obungu VH, Lee Burns A, Agarwal SK, Chandrasekharapa SC, Adelstein RS, Marx SJ. Menin, a tumor suppressor, associates with nonmuscle myosin II-A heavy chain. Oncogene 2003;22(41):6347-58.
44. Lopez-Egido J, Cunningham J, Berg M, Oberg K, Bongcam-Rudloff E, Gobl A. Menin's interaction with glial fibrillary acidic protein and vimentin suggests a role for the intermediate filament network in regulating menin activity. Exp Cell Res 2002;278(2):175-83.
45. Poisson A, Zablewska B, Gaudray P. Menin interacting proteins as clues toward the understanding of multiple endocrine neoplasia type 1. Cancer Lett 2003;189(1):1-10.
46. Lin SY, Elledge SJ. Multiple tumor suppressor pathways negatively regulate telomerase. Cell 2003;113(7):881-9.
47. Kim YS, Burns AL, Goldsmith PK, Heppner C, Park SY, Chandrasekharappa SC, et al. Stable overexpression of MEN1 suppresses tumorigenicity of RAS. Oncogene 1999;18(43):5936-42.
48. Stalberg P, Grimfjard P, Santesson M, Zhou Y, Lindberg D, Gobl A, et al. Transfection of the multiple endocrine neoplasia type 1 gene to a human endocrine pancreatic tumor cell line inhibits cell growth and affects expression of JunD, delta-like protein 1/preadipocyte factor-1, proliferating cell nuclear antigen, and QM/Jif-1. J Clin Endocrinol Metab 2004;89(5):2326-37.
49. Yumita W, Ikeo Y, Yamauchi K, Sakurai A, Hashizume K. Suppression of insulin-induced AP-1 transactivation by menin accompanies inhibition of c-Fos induction. Int J Cancer 2003;103(6):738-44.
50. Boikos SA, Stratakis CA. Carney complex: the first 20 years. Curr Opin Oncol 2007;19(1):24-9.
51. Kirschner LS, Carney JA, Pack SD, Taymans SE, Giatzakis C, Cho YS, 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(1):89-92.
52. Bossis I, Voutetakis A, Matyakhina L, Pack S, Abu-Asab M, Bourdeau I, et al. A pleiomorphic GH pituitary adenoma from a Carney complex patient displays universal allelic loss at the protein kinase A regulatory subunit 1A (PRKARIA) locus. J Med Genet 2004;41(8):596-600.
53. Stratakis CA, Carney JA, Lin JP, Papanicolaou DA, Karl M, Kastner DL, et al. Carney complex, a familial multiple neoplasia and lentiginosis syndrome. Analysis of 11 kindreds and linkage to the short arm of chromosome 2. J Clin Invest 1996;97(3):699-705.
54. Boikos SA, Stratakis CA. Pituitary pathology in patients with Carney Complex: growth-hormone producing hyperplasia or tumors and their association with other abnormalities. Pituitary 2006;9(3):203-9.
55. Pack SD, Qin LX, Pak E, Wang Y, Ault DO, Mannan P, et al. Common genetic changes in hereditary and sporadic pituitary adenomas detected by comparative genomic hybridization. Genes Chromosomes Cancer 2005;43(1):72-82.
56. Stergiopoulos SG, Abu-Asab MS, Tsokos M, Stratakis CA. Pituitary pathology in Carney complex patients. Pituitary 2004;7(2):73-82.
57. Stratakis CA, Matyakhina L, Courkoutsakis N, Patronas N, Voutetakis A, Stergiopoulos S, et al. Pathology and molecular genetics of the pituitary gland in patients with the 'complex of spotty skin pigmentation, myxomas, endocrine overactivity and schwannomas' (Carney complex). Front Horm Res 2004;32:253-64.
58. Kirschner LS, Sandrini F, Monbo J, Lin JP, Carney JA, Stratakis CA. Genetic heterogeneity and spectrum of mutations of the PRKAR1A gene in patients with the Carney complex. Hum Mol Genet 2000;9(20):3037-46.
59. Groussin L, Kirschner LS, Vincent-Dejean C, Perlemoine K, Jullian E, Delemer B, et al. Molecular analysis of the cyclic AMP-dependent protein kinase A (PKA) regulatory subunit 1A (PRKAR1A) gene in patients with Carney complex and primary pigmented nodular adrenocortical disease (PPNAD) reveals novel mutations and clues for pathophysiology: augmented PKA signaling is associated with adrenal tumorigenesis in PPNAD. Am J Hum Genet 2002;71(6):1433-42.
60. Robinson-White AJ, Leitner WW, Aleem E, Kaldis P, Bossis I, Stratakis CA. PRKAR1A inactivation leads to increased proliferation and decreased apoptosis in human B lymphocytes. Cancer Res 2006;66(21):10603-12.
61. Robinson-White A, Meoli E, Stergiopoulos S, Horvath A, Boikos S, Bossis I, et al. PRKAR1A Mutations and protein kinase A interactions with other signaling pathways in the adrenal cortex. J Clin Endocrinol Metab 2006;91(6):2380-8.
62. Bossis I, Stratakis CA. Minireview: PRKAR1A: normal and abnormal functions. Endocrinology 2004;145(12):5452-8.
63. Greene E, Horvath A, Nesterova M, Giatzakis C, Bossis I, Stratakis C. In vitro functional studies of naturally occurring pathogenic PRKAR1A mutations that are not subject to nonsense mRNA decay. Hum Mutat 2008 (in press).
64. Horvath A, Bossis I, Giatzakis C, Levine E, Weinberg F, Meoli E, et al. Large deletions of the PRKAR1A gene in Carney complex: phenotype correlations and implications for laboratory and diagnostic testing. Clin Cancer Res 2008 (in press).
65. Amieux PS, Howe DG, Knickerbocker H, Lee DC, Su T, Laszlo GS, et al. Increased basal cAMP-dependent protein kinase activity inhibits the formation of mesoderm-derived structures in the developing mouse embryo. J Biol Chem 2002;277(30):27294-304.
66. Griffin KJ, Kirschner LS, Matyakhina L, Stergiopoulos SG, Robinson-White A, Lenherr SM, et al. A transgenic mouse bearing an antisense construct of regulatory subunit type 1A of protein kinase A develops endocrine and other tumours: comparison with Carney complex and other PRKAR1A induced lesions. J Med Genet 2004;41(12):923-31.
67. Kirschner LS, Kusewitt DF, Matyakhina L, Towns WH 2nd, Carney JA, et al. A mouse model for the Carney complex tumor syndrome develops neoplasia in cyclic AMP-responsive tissues. Cancer Res 2005;65(11):4506-14.
68. Pecori Giraldi F, Mizobuchi M, Horowitz ZD, Downs TR, Aleppo G, Kier A, et al. Development of neuroepithelial tumors of the adrenal medulla in transgenic mice expressing a mouse hypothalamic growth hormone-releasing hormone promoter-simian virus-40 T-antigen fusion gene. Endocrinology 1994;134(3):1219-24.
69. Kovacs K, Horvath E, Thorner MO, Rogol AD. Mammosomatotroph hyperplasia associated with acromegaly and hyperprolactinemia in a patient with the McCune-Albright syndrome. A histologic, immunocytologic and ultrastructural study of the surgically-removed adenohypophysis. Virchows Arch A Pathol Anat Histopathol 1984;403(1):77-86.
70. Cuttler L, Jackson JA, Saeed uz-Zafar M, Levitsky LL, Mellinger RC, Frohman LA. Hypersecretion of growth hormone and prolactin in McCune-Albright syndrome. J Clin Endocrinol Metab 1989;68(6):1148-54.
71. Pack SD, Kirschner LS, Pak E, Zhuang Z, Carney JA, Stratakis CA. Genetic and histologic studies of somatomammotropic pituitary tumors in patients with the "complex of spotty skin pigmentation, myxomas, endocrine overactivity and schwannomas" (Carney complex). J Clin Endocrinol Metab 2000;85(10):3860-5.
72. Lee JS, FitzGibbon E, Butman JA, Dufresne CR, Kushner H, Wientroub S, et al. Normal vision despite narrowing of the optic canal in fibrous dysplasia. N Engl J Med 2002;347(21):1670-6.
73. Kaushik S, Smoker WR, Frable WJ. Malignant transformation of fibrous dysplasia into chondroblastic osteosarcoma. Skeletal Radiol 2002;31(2):103-6.
74. Akintoye SO, Kelly MH, Brillante B, Cherman N, Turner S, Butman JA, et al. Pegvisomant for the treatment of gsp-mediated growth hormone excess in patients with McCune-Albright syndrome. J Clin Endocrinol Metab 2006;91(8):2960-6.
75. Galland F, Kamenicky P, Affres H, Reznik Y, Pontvert D, Le Bouc Y, et al. McCune-Albright syndrome and acromegaly: effects of hypothalamopituitary radiotherapy and/or pegvisomant in somatostatin analog-resistant patients. J Clin Endocrinol Metab 2006;91(12):4957-61.
76. Vallar L, Spada A, Giannattasio G. Altered Gs and adenylate cyclase activity in human GH-secreting pituitary adenomas. Nature 1987;330(6148):566-8.
77. Weinstein LS, Shenker A, Gejman PV, Merino MJ, Friedman E, Spiegel AM. Activating mutations of the stimulatory G protein in the McCune-Albright syndrome. N Engl J Med 1991;325(24):1688-95.
78. Hayward BE, Barlier A, Korbonits M, Grossman AB, Jacquet P, Enjalbert A, et al. Imprinting of the G(s)alpha gene GNAS1 in the pathogenesis of acromegaly. J Clin Invest 2001;107(6):R31-6.
79. Mantovani G, Ballare E, Giammona E, Beck-Peccoz P, Spada A. The gsalpha gene: predominant maternal origin of transcription in human thyroid gland and gonads. J Clin Endocrinol Metab 2002;87(10):4736-40.
80. Yamasaki H, Mizusawa N, Nagahiro S, Yamada S, Sano T, Itakura M, et al. GH-secreting pituitary adenomas infrequently contain inactivating mutations of PRKAR1A and LOH of 17q23-24. Clin Endocrinol (Oxf) 2003;58(4):464-70.
81. Sandrini F, Kirschner LS, Bei T, Farmakidis C, Yasufuku-Takano J, Takano K, et al. PRKAR1A, one of the Carney complex genes, and its locus (17q22-24) are rarely altered in pituitary tumours outside the Carney complex. J Med Genet 2002;39(12):e78.
82. Esapa CT, Harris PE. Mutation analysis of protein kinase A catalytic subunit in thyroid adenomas and pituitary tumours. Eur J Endocrinol 1999;141(4):409-12.
83. Riminucci M, Collins MT, Lala R, Corsi A, Matarazzo P, Gehron Robey P, et al. An R201H activating mutation of the GNAS1 (Gsalpha) gene in a corticotroph pituitary adenoma. Mol Pathol 2002;55(1):58-60.
84. Lyons J, Landis CA, Harsh G, Vallar L, Grunewald K, Feichtinger H, et al. Two G protein oncogenes in human endocrine tumors. Science 1990;249(4969):655- 9.
85. Williamson EA, Daniels M, Foster S, Kelly WF, Kendall-Taylor P, Harris PE. Gs alpha and Gi2 alpha mutations in clinically non-functioning pituitary tumours. Clin Endocrinol (Oxf) 1994;41(6):815-20.
86. Gicquel C, Dib A, Bertagna X, Amselem S, Le Bouc Y. Oncogenic mutations of alpha-Gi2 protein are not determinant for human adrenocortical tumourigenesis. Eur J Endocrinol 1995;133(2):166-72.
87. Petersenn S, Heyens M, Ludecke DK, Beil FU, Schulte HM. Absence of somatostatin receptor type 2 A mutations and gip oncogene in pituitary somatotroph adenomas. Clin Endocrinol (Oxf) 2000;52(1):35-42.
88. Alvaro V, Levy L, Dubray C, Roche A, Peillon F, Querat B, et al. Invasive human pituitary tumors express a point-mutated alpha-protein kinase-C. J Clin Endocrinol Metab 1993;77(5):1125-9.
89. Schiemann U, Assert R, Moskopp D, Gellner R, Hengst K, Gullotta F, et al. Analysis of a protein kinase C-alpha mutation in human pituitary tumours. J Endocrinol 1997;153(1):131-7.
90. Verloes A, Stevenaert A, Teh BT, Petrossians P, Beckers A. Familial acromegaly: case report and review of the literature. Pituitary 1999;1(3-4):273-7.
91. Beckers A, Daly AF. The clinical, pathological, and genetic features of familial isolated pituitary adenomas. Eur J Endocrinol 2007;157(4):371-82.
92. Vierimaa O, Georgitsi M, Lehtonen R, Vahteristo P, Kokko A, Raitila A, et al. Pituitary adenoma predisposition caused by germline mutations in the AIP gene. Science 2006;312(5777):1228-30.
93. Daly AF, Vanbellinghen JF, Khoo SK, Jaffrain-Rea ML, Naves LA, Guitelman MA, et al. Aryl hydrocarbon receptor-interacting protein gene mutations in familial isolated pituitary adenomas: analysis in 73 families. J Clin Endocrinol Metab 2007;92(5):1891-6.
94. Petrulis JR, Perdew GH. The role of chaperone proteins in the aryl hydrocarbon receptor core complex. Chem Biol Interact 2002;141(1-2):25-40.
95. Meyer BK, Petrulis JR, Perdew GH. Aryl hydrocarbon (Ah) receptor levels are selectively modulated by hsp90-associated immunophilin homolog XAP2. Cell Stress Chaperones 2000;5(3):243-54.
96. Bell DR, Poland A. Binding of aryl hydrocarbon receptor (AhR) to AhR-interacting protein. The role of hsp90. J Biol Chem 2000;275(46):36407-14.
97. Meyer BK, Perdew GH. Characterization of the AhR-hsp90-XAP2 core complex and the role of the immunophilin-related protein XAP2 in AhR stabilization. Biochemistry 1999;38(28):8907-17.
98. Beckers A, Daly AF. The clinical, pathological, and genetic features of familial isolated pituitary adenomas. Eur J Endocrinol 2007;157(4):371-82.
99. Khaliq S, Abid A, Hameed A, Anwar K, Mohyuddin A, Ismail M, et al. Gene symbol: AIPL1. Disease: LCA4. Hum Genet 2005;116(6):542.
100. Persani L, Borgato S, Lania A, Filopanti M, Mantovani G, Conti M, et al. Relevant cAMP-specific phosphodiesterase isoforms in human pituitary: effect of Gs(alpha) mutations. J Clin Endocrinol Metab 2001;86(8):3795-800.
101. Gonsky R, Herman V, Melmed S, Fagin J. Transforming DNA sequences present in human prolactin-secreting pituitary tumors. Mol Endocrinol 1991;5(11):1687-95.
102. Ezzat S, Zheng L, Asa SL. Pituitary tumor-derived fibroblast growth factor receptor 4 isoform disrupts neural cell-adhesion molecule/N-cadherin signaling to diminish cell adhesiveness: a mechanism underlying pituitary neoplasia. Mol Endocrinol 2004;18(10):2543-52.
103. Ezzat S, Yu S, Asa SL. Ikaros isoforms in human pituitary tumors: distinct localization, histone acetylation, and activation of the 5′ fibroblast growth factor receptor-4 promoter. Am J Pathol 2003;163(3):1177-84.
104. Ezzat S, Zheng L, Zhu XF, Wu GE, Asa SL. Targeted expression of a human pituitary tumor-derived isoform of FGF receptor-4 recapitulates pituitary tumorigenesis. J Clin Invest 2002;109(1):69-78.
105. Yu R, Melmed S. Pituitary tumor transforming gene: an update. Front Horm Res 2004;32:175-85.
106. Zou H, McGarry TJ, Bernal T, Kirschner MW. Identification of a vertebrate sister-chromatid separation inhibitor involved in transformation and tumorigenesis. Science 1999;285(5426):418-22.
107. McCabe CJ, Boelaert K, Tannahill LA, Heaney AP, Stratford AL, Khaira JS, et al. Vascular endothelial growth factor, its receptor KDR/Flk-1, and pituitary tumor transforming gene in pituitary tumors. J Clin Endocrinol Metab 2002;87(9):4238-44.
108. Donangelo I, Marcos HP, Araujo PB, Marcondes J, Filho PN, Gadelha M, et al. Expression of retinoblastoma protein in human growth hormone-secreting pituitary adenomas. Endocr Pathol 2005;16(1):53-62.
109. Honda S, Tanaka-Kosugi C, Yamada S, Sano T, Matsumoto T, Itakura M, et al. Human pituitary adenomas infrequently contain inactivation of retinoblastoma 1 gene and activation of cyclin dependent kinase 4 gene. Endocr J 2003;50(3):309-18.
110. Zhu J, Leon SP, Beggs AH, Busque L, Gilliland DG, Black PM. Human pituitary adenomas show no loss of heterozygosity at the retinoblastoma gene locus. J Clin Endocrinol Metab 1994;78(4):922-7.
111. Loffler KA, Biondi CA, Gartside MG, Serewko-Auret MM, Duncan R, Tonks ID, et al. Lack of augmentation of tumor spectrum or severity in dual heterozygous Men1 and Rb1 knockout mice. Oncogene 2007;26(27):4009-17.
112. Takahashi C, Contreras B, Iwanaga T, Takegami Y, Bakker A, Bronson RT, et al. Nras loss induces metastatic conversion of Rb1-deficient neuroendocrine thyroid tumor. Nat Genet 2006;38(1):118-23.
113. Zhang X, Sun H, Danila DC, Johnson SR, Zhou Y, Swearingen B, et al. Loss of expression of GADD45 gamma, a growth inhibitory gene, in human pituitary adenomas: implications for tumorigenesis. J Clin Endocrinol Metab 2002;87(3):1262-7.
114. Zhao J, Dahle D, Zhou Y, Zhang X, Klibanski A. Hypermethylation of the promoter region is associated with the loss of MEG3 gene expression in human pituitary tumors. J Clin Endocrinol Metab 2005;90(4):2179-86.
115. Pagotto U, Arzberger T, Theodoropoulou M, Grubler Y, Pantaloni C, Saeger W, et al. The expression of the antiproliferative gene ZAC is lost or highly reduced in nonfunctioning pituitary adenomas. Cancer Res 2000;60(24):6794-9.