Review paper: Origin and molecular pathology of adrenocortical neoplasms

Veterinary Pathology

Volumn 46, Issue 2, 2009, Pages 194-210

  Bielinska, M ^a   Parviainen, H ^b,c   Kiiveri, S ^b   Heikinheimo, M ^a,b,c   Wilson, D B ^a  

^a WASHINGTON UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF HELSINKI   (Finland)

^c UNIVERSITY OF HELSINKI   (Finland)

Author keywords

Adrenal cortex neoplasms; Animal; Ferrets; Models; Orchiectomy; Ovariectomy; Steroidogenesis

Indexed keywords

ANIMALIA; MUSTELA;

ADRENAL CORTEX; ADRENAL CORTEX TUMOR; ANIMAL; ANIMAL DISEASE; CATTLE; CYTOLOGY; FERRET; GOAT; GROWTH, DEVELOPMENT AND AGING; HAMSTER; HUMAN; MOUSE; PATHOLOGY; REVIEW;

ADRENAL CORTEX; ADRENAL CORTEX NEOPLASMS; ANIMALS; CATTLE; CRICETINAE; FERRETS; GOATS; HUMANS; MICE;

EID: 67650870201     PISSN: 03009858     EISSN: 15442217     Source Type: Journal    
DOI: 10.1354/vp.46-2-194     Document Type: Review

References (165)

1. Achermann JC, Meeks JJ, Jameson JL: Phenotypic spectrum of mutations in DAX-1 and SF-1. Mol Cell Endocrinol 185:17-25, 2001
2. Almeida MQ, Latronico AC: The molecular pathogenesis of childhood adrenocortical tumors. Horm Metab Res 39:461-466, 2007
3. Altman NH, Streett CS, Terner JY: Castration and its relationship to tumors of the adrenal gland in the goat. Am J Vet Res 30:583-589, 1969
4. Artandi SE, Attardi LD: Pathways connecting telomeres and p53 in senescence, apoptosis, and cancer. Biochem Biophys Res Commun 331:881-890, 2005
5. Auchus RJ: Overview of dehydroepiandrosterone biosynthesis. Semin Reprod Med 22:281-288, 2004
6. Bailey SM, Murnane JP: Telomeres, chromosome instability and cancer. Nucleic Acids Res 34:2408-2417, 2006
7. Barlaskar FM, Hammer GD: The molecular genetics of adrenocortical carcinoma. Rev Endocr Metab Disord 8:343-348, 2007
8. Ben-David S, Zuckerman-Levin N, Epelman M, Shen-Orr Z, Levin M, Sujov P, Hochberg Z: Parturition itself is the basis for fetal adrenal involution. J Clin Endocrinol Metab 92:93-97, 2007
9. Bernichtein S, Petretto E, Jamieson S, Goel A, Aitman TJ, Mangion JM, Huhtaniemi IT: Adrenal gland tumorigenesis after gonadectomy in mice is a complex genetic trait driven by epistatic loci. Endocrinology 149:651-661, 2007
10. Bertherat J, Groussin L, Sandrini F, Matyakhina L, Bei T, Stergiopoulos S, Papageorgiou T, Bourdeau I, Kirschner LS, Vincent-Dejean C, Perlemoine K, Gicquel C, Bertagna X, Stratakis CA: Molecular and functional analysis of PRKAR1A and its locus (17q22-24) in sporadic adrenocortical tumors: 17q losses, somatic mutations, and protein kinase A expression and activity. Cancer Res 63:5308-5319, 2003
11. Bertherat J, Mosnier-Pudar H, Bertagna X: Adrenal incidentalomas. Curr Opin Oncol 14:58-63, 2002
12. Beuschlein F, Looyenga BD, Bleasdale SE, Mutch C, Bavers DL, Parlow AF, Nilson JH, Hammer GD: Activin induces x-zone apoptosis that inhibits luteinizing hormone-dependent adrenocortical tumor formation in inhibin-deficient mice. Mol Cell Biol 23:3951-3964, 2003
13. Beuschlein F, Looyenga BD, Reincke M, Hammer GD: Role of the inhibin/activin system and luteinizing hormone in adrenocortical tumorigene-sis. Horm Metab Res 36:392-396, 2004
14. Beuschlein F, Mutch C, Bavers DL, Ulrich-Lai YM, Engeland WC, Keegan C, Hammer GD: Steroidogenic factor-1 is essential for compensatory adrenal growth following unilateral adrenalectomy. Endocrinology 143:3122-3135, 2002
15. Beuschlein F, Reincke M: Adrenocortical tumorigenesis. Ann N Y Acad Sci 1088:319-334, 2006
16. Beuschlein F, Reincke M, Karl M, Travis WD, Jaursch-Hancke C, Abdelhamid S, Chrousos GP, Allolio B: Clonal composition of human adrenocortical neoplasms. Cancer Res 54:4927-4932, 1994
17. Bielinska M, Genova E, Boime I, Parviainen H, Kiiveri S, Leppaluoto J, Rahman N, Heikinheimo M, Wilson DB: Gonadotropin-induced adrenocortical neoplasia in NU/J nude mice. Endocrinology 146:3975-3984, 2005
18. Bielinska M, Kiiveri S, Parviainen H, Mannisto S, Heikinheimo M, Wilson DB: Gonadectomy-induced adrenocortical neoplasia in the domestic ferret (Mustela putorius furo) and laboratory mouse. Vet Pathol 43:97-117, 2006
19. Blaker H, Sutter C, Kadmon M, Otto HF, Von Knebel-Doeberitz M, Gebert J, Helmke BM: Analysis of somatic APC mutations in rare extra-colonic tumors of patients with familial adenoma-tous polyposis coli. Genes Chromosomes Cancer 41:93-98, 2004
20. Blanes A, az-Cano SJ: DNA and kinetic heterogeneity during the clonal evolution of adrenocortical proliferative lesions. Hum Pathol 37:1295-1303, 2006
21. Boulle N, Gicquel C, Logie A, Christol R, Feige JJ, Le BY: Fibroblast growth factor-2 inhibits the maturation of pro-insulin-like growth factor-II (Pro-IGF-II) and the expression of insulin-like growth factor binding protein-2 (IGFBP-2) in the human adrenocortical tumor cell line NCI-H295R. Endocrinology 141:3127-3136, 2000
22. Boulle N, Logie A, Gicquel C, Perin L, Le BY: Increased levels of insulin-like growth factor II (IGF-II) and IGF-binding protein-2 are associated with malignancy in sporadic adrenocortical tumors. J Clin Endocrinol Metab 83:1713-1720, 1998
23. Bourdeau I, Antonini SR, Lacroix A, Kirschner LS, Matyakhina L, Lorang D, Libutti SK, Stratakis CA: Gene array analysis of macronodular adrenal hyperplasia confirms clinical heterogeneity and identifies several candidate genes as molecular mediators. Oncogene 23:1575-1585, 2004
24. Brand C, Cherradi N, Defaye G, Chinn A, Chambaz EM, Feige JJ, Bailly S: Transforming growth factor b1 decreases cholesterol supply to mitochondria via repression of steroidogenic acute regulatory protein expression. J Biol Chem 273: 6410-6416, 1998
25. Brunt LM, Moley JF: Adrenal incidentaloma. World J Surg 25:905-913, 2001
26. Caspary T, Cleary MA, Perlman EJ, Zhang P, Elledge SJ, Tilghman SM: Oppositely imprinted genes p57(Kip2) and Igf2 interact in a mouse model for Beckwith-Wiedemann syndrome. Genes Dev 13:3115-3124, 1999
27. Chen M, Hawks CL, Huang Q, Sun B, Hornsby PJ: Telomerase is not required for experimental tumorigenesis of human and bovine adrenocortical cells. Endocr Res 30:555-565, 2004
28. Chen M, Hornsby PJ: Adenovirus-delivered DKK3/WNT4 and steroidogenesis in primary cultures of adrenocortical cells. Horm Metab Res 38:549-555, 2006
29. Chida D, Nakagawa S, Nagai S, Sagara H, Katsumata H, Imaki T, Suzuki H, Mitani F, Ogishima T, Shimizu C, Kotaki H, Kakuta S, Sudo K, Koike T, Kubo M, Iwakura Y: Melanocortin 2 receptor is required for adrenal gland development, steroidogenesis, and neonatal gluconeogenesis. Proc Natl Acad Sci USA 104:18205-18210, 2007
30. Chin L, Artandi SE, Shen Q, Tam A, Lee SL, Gottlieb GJ, Greider CW, DePinho RA: p53 deficiency rescues the adverse effects of telomere loss and cooperates with telomere dysfunction to accelerate carcinogenesis. Cell 97:527-538, 1999
31. Choi J, Southworth LK, Sarin KY, Venteicher AS, Ma W, Chang W, Cheung P, Jun S, Artandi MK, Shah N, Kim SK, Artandi SE: TERT promotes epithelial proliferation through transcriptional control of a Myc- and Wnt-related developmental program. PLoS Genet 4:e10, 2008
32. Cohen SB, Graham ME, Lovrecz GO, Bache N, Robinson PJ, Reddel RR: Protein composition of catalytically active human telomerase from immortal cells. Science 315:1850-1853, 2007
33. Coulter CL: Fetal adrenal development: insight gained from adrenal tumors. Trends Endocrinol Metab 16:235-242, 2005
34. de Fraipont F, El Atifi M, Cherradi N, Le MG, Defaye G, Houlgatte R, Bertherat J, Bertagna X, Plouin PF, Baudin E, Berger F, Gicquel C, Chabre O, Feige JJ: Gene expression profiling of human adrenocortical tumors using complementary deox-yribonucleic acid microarrays identifies several candidate genes as markers of malignancy. J Clin Endocrinol Metab 90:1819-1829, 2005
35. de Fraipont F, El Atifi M, Gicquel C, Bertagna X, Chambaz EM, Feige JJ: Expression of the angiogenesis markers vascular endothelial growth factor-A, thrombospondin-1, and platelet-derived endothelial cell growth factor in human sporadic adrenocortical tumors: correlation with genotypic alterations. J Clin Endocrinol Metab 85:4734-4741, 2000
36. DeBaun MR, Niemitz EL, McNeil DE, Brandenburg SA, Lee MP, Feinberg AP: Epigenetic alterations of H19 and LIT1 distinguish patients with Beckwith-Wiedemann syndrome with cancer and birth defects. Am J Hum Genet 70:604-611, 2002
37. DeChiara TM, Robertson EJ, Efstratiadis A: Parental imprinting of the mouse insulin-like growth factor II gene. Cell 64:849-859, 1991
38. Doghman M, Cazareth J, Lalli E: The Tcf/b-catenin antagonist PKF115-584 inhibits proliferation of adrenocortical carcinoma cells. J Clin Endocrinol Metab 93:3222-3225, 2008
39. Doghman M, Karpova T, Rodrigues GA, Arhatte M, De MJ, Cavalli LR, Virolle V, Barbry P, Zambetti GP, Figueiredo BC, Heckert LL, Lalli E: Increased steroidogenic factor-1 dosage triggers adrenocortical cell proliferation and cancer. Mol Endocrinol 21:2968-2987, 2007
40. Edgren M, Eriksson B, Wilander E, Westlin JE, Nilsson S, Oberg K: Biological characteristics of adrenocortical carcinoma: a study of p53, IGF, EGF-r, Ki-67 and PCNA in 17 adrenocortical carcinomas. Anticancer Res 17:1303-1309, 1997
41. Else T, Giordano TJ, Hammer GD: Evaluation of telomere length maintenance mechanisms in adre-nocortical carcinoma. J Clin Endocrinol Metab 93:1442-1449, 2008
42. Else T, Hammer GD: Genetic analysis of adrenal absence: agenesis and aplasia. Trends Endocrinol Metab 16:458-468, 2005
43. Else T, Theisen BK, Wu Y, Hutz JE, Keegan CE, Hammer GD, Ferguson DO: Tpp1/Acd maintains genomic stability through a complex role in telomere protection. Chromosome Res 15:1001-1013, 2007
44. Fassnacht M, Weismann D, Ebert S, Adam P, Zink M, Beuschlein F, Hahner S, Allolio B: AKT is highly phosphorylated in pheochromocytomas but not in benign adrenocortical tumors. J Clin Endocrinol Metab 90:4366-4370, 2005
45. Feinberg AP: A genetic approach to cancer epigenetics. Cold Spring Harb Symp Quant Biol 70:335-341, 2005
46. Feinberg AP: Phenotypic plasticity and the epigenetics of human disease. Nature 447:433-440, 2007
47. Feinberg AP, Ohlsson R, Henikoff S: The epigenetic progenitor origin of human cancer. Nat Rev Genet 7:21-33, 2006
48. Fekete E, Woolley G, Little CC: Histological changes following ovariectomy in mice: I. dba high tumor strain. J Exp Med 74:1-8, 1941
49. Feldman EC, Nelson RW: Comparative aspects of Cushing's syndrome in dogs and cats. Endocrinol Metab Clin North Am 23:671-691, 1994
50. Figueiredo BC, Cavalli LR, Pianovski MA, Lalli E, Sandrini R, Ribeiro RC, Zambetti G, DeLacerda L, Rodrigues GA, Haddad BR: Amplification of the steroidogenic factor 1 gene in childhood adrenocortical tumors. J Clin Endocrinol Metab 90:615-619, 2005
51. Figueiredo BC, Sandrini R, Zambetti GP, Pereira RM, Cheng C, Liu W, Lacerda L, Pianovski MA, Michalkiewicz E, Jenkins J, Rodriguez-Galindo C, Mastellaro MJ, Vianna S, Watanabe F, Sandrini F, Arram SB, Boffetta P, Ribeiro RC: Penetrance of adrenocortical tumours associated with the germ-line TP53 R337H mutation. J Med Genet 43:91-96, 2006
52. Figueiredo BC, Stratakis CA, Sandrini R, DeLa-cerda L, Pianovsky MA, Giatzakis C, Young HM, Haddad BR: Comparative genomic hybridization analysis of adrenocortical tumors of childhood. J Clin Endocrinol Metab 84:1116-1121, 1999
53. Flores I, Cayuela ML, Blasco MA: Effects of telomerase and telomere length on epidermal stem cell behavior. Science 309:1253-1256, 2005
54. Fottner C, Hoeflich A, Wolf E, Weber MM: Role of the insulin-like growth factor system in adrenocortical growth control and carcinogenesis. Horm Metab Res 36:397-405, 2004
55. Fox JG, Marini RP: Diseases of the Endocrine System. In: Biology and Diseases of the Ferret, ed. Fox JG, pp. 291-305. Lea & Febiger, Philadelphia, PA, 1998
56. Gicquel C, Bertagna X, Gaston V, Coste J, Louvel A, Baudin E, Bertherat J, Chapuis Y, Duclos JM, Schlumberger M, Plouin PF, Luton JP, Le BY: Molecular markers and long-term recurrences in a large cohort of patients with sporadic adrenocortical tumors. Cancer Res 61:6762-6767, 2001
57. Gicquel C, Leblond-Francillard M, Bertagna X, Louvel A, Chapuis Y, Luton JP, Girard F, Le BY: Clonal analysis of human adrenocortical carcinomas and secreting adenomas. Clin Endocrinol (Oxf) 40:465-477, 1994
58. Goto M, Piper HK, Marcos J, Wood PJ, Wright S, Postle AD, Cameron IT, Mason JI, Wilson DI, Hanley NA: In humans, early cortisol biosynthesis provides a mechanism to safeguard female sexual development. J Clin Invest 116:953-960, 2006
59. Greider CW: Telomeres. Curr Opin Cell Biol 3: 444-451, 1991
60. Gummow BM, Winnay JN, Hammer GD: Convergence of Wnt signaling and steroidogenic factor-1 (SF-1) on transcription of the rat inhibin alpha gene. J Biol Chem 278:26572-26579, 2003
61. Guo W, Mason JS, Stone CG, Jr., Morgan SA, Madu SI, Baldini A, Lindsay EA, Biesecker LG, Copeland KC, Horlick MN: Diagnosis of X-linked adrenal hypoplasia congenita by mutation analysis of the DAX1 gene. JAMA 274:324-330, 1995
62. Haluska P, Shaw HM, Batzel GN, Yin D, Molina JR, Molife LR, Yap TA, Roberts ML, Sharma A, Gualberto A, Adjei AA, de Bono JS: Phase I dose escalation study of the anti insulin-like growth factor-I receptor monoclonal antibody CP-751,871 in patients with refractory solid tumors. Clin Cancer Res 13:5834-5840, 2007
63. Harrington L, Robinson MO: Telomere dysfunction: multiple paths to the same end. Oncogene 21:592-597, 2002
64. He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW: Identification of c-MYC as a target of the APC pathway. Science 281:1509-1512, 1998
65. Heikkila M, Peltoketo H, Leppaluoto J, Ilves M, Vuolteenaho O, Vainio S: Wnt-4 deficiency alters mouse adrenal cortex function, reducing aldosterone production. Endocrinology 143:4358-4365, 2002
66. Heppner C, Reincke M, Agarwal SK, Mora P, Allolio B, Burns AL, Spiegel AM, Marx SJ: MEN1 gene analysis in sporadic adrenocortical neoplasms. J Clin Endocrinol Metab 84:216-219, 1999
67. Hershkovitz L, Beuschlein F, Klammer S, Krup M, Weinstein Y: Adrenal 20alpha-hydroxysteroid de-hydrogenase in the mouse catabolizes progesterone and 11-deoxycorticosterone and is restricted to the X-zone. Endocrinology 148:976-988, 2007
68. Heyerdahl SL, Boikos S, Horvath A, Giatzakis C, Bossis I, Stratakis CA: Protein kinase A subunit expression is altered in bloom syndrome fibroblasts and the BLM protein is increased in adrenocortical hyperplasias: inverse findings for BLM and PRKAR1A. Horm Metab Res 40:391-397, 2008
69. Hockemeyer D, Palm W, Else T, Daniels JP, Takai KK, Ye JZ, Keegan CE, de LT, Hammer GD: Telomere protection by mammalian Pot1 requires interaction with Tpp1. Nat Struct Mol Biol 14:754-761, 2007
70. Holmes RL: The adrenal glands of the ferret. J Anat 95:325-336, 1961
71. Horvath A, Giatzakis C, Tsang K, Greene E, Osorio P, Boikos S, Libe R, Patronas Y, Robinson-White A, Remmers E, Bertherat J, Nesterova M, Stratakis CA: A cAMP-specific phosphodiesterase (PDE8B) that is mutated in adrenal hyperplasia is expressed widely in human and mouse tissues: a novel PDE8B isoform in human adrenal cortex. Eur J Hum Genet 16:1245-1253, 2008
72. Horvath A, Stratakis CA: Unraveling the molecular basis of micronodular adrenal hyperplasia. Curr Opin Endocrinol Diabetes Obes 15:227-233, 2008
73. Hu MC, Chou SJ, Huang YY, Hsu NC, Li H, Chung BC: Tissue-specific, hormonal, and developmental regulation of SCC-LacZ expression in transgenic mice leads to adrenocortical zone characterization. Endocrinology 140:5609-5618, 1999
74. Igaz P, Wiener Z, Szabó P, Falus A, Gaillard RC, Horányi J, Rácz K, Tulassay Z: Functional genomics approaches for the study of sporadic adrenal tumor pathogenesis: clinical implications. J Steroid Biochem Mol Biol 101:87-96, 2006
75. Jeays-Ward K, Hoyle C, Brennan J, Dandonneau M, Alldus G, Capel B, Swain A: Endothelial and steroidogenic cell migration are regulated by WNT4 in the developing mammalian gonad. Development 130:3663-3670, 2003
76. Kamio T, Shigematsu K, Sou H, Kawai K, Tsuchiyama H: Immunohistochemical expression of epidermal growth factor receptors in human adrenocortical carcinoma. Hum Pathol 21:277-282, 1990
77. Kaneda A, Wang CJ, Cheong R, Timp W, Onyango P, Wen B, Iacobuzio-Donahue CA, Ohlsson R, Andraos R, Pearson MA, Sharov AA, Longo DL, Ko MS, Levchenko A, Feinberg AP: Enhanced sensitivity to IGF-II signaling links loss of imprinting of IGF2 to increased cell proliferation and tumor risk. Proc Natl Acad Sci USA 104:20926-20931, 2007
78. Kawabe K, Shikayama T, Tsuboi H, Oka S, Oba K, Yanase T, Nawata H, Morohashi K: Dax-1 as one of the target genes of Ad4BP/SF-1. Mol Endocrinol 13:1267-1284, 1999
79. Keegan CE, Hammer GD: Recent insights into organogenesis of the adrenal cortex. Trends Endocrinol Metab 13:200-208, 2002
80. Keegan CE, Hutz JE, Else T, Adamska M, Shah SP, Kent AE, Howes JM, Beamer WG, Hammer GD: Urogenital and caudal dysgenesis in adreno-cortical dysplasia (acd) mice is caused by a splicing mutation in a novel telomeric regulator. Hum Mol Genet 14:113-123, 2005
81. Keeney DS, Jenkins CM, Waterman MR: Developmentally regulated expression of adrenal 17a-hydroxylase cytochrome P450 in the mouse embryo. Endocrinology 136:4872-4879, 1995
82. Kempná P, Flück CE: Adrenal gland development and defects. Best Pract Res Clin Endocrinol Metab 22:77-93, 2008
83. Keyes PH: Adreno-cortical changes in Syrian hamsters following gonadectomy. Endocrinology 44:274-277, 1949
84. Kim AC, Hammer GD: Adrenocortical cells with stem/progenitor cell properties: recent advances. Mol Cell Endocrinol 265-266:10-16, 2007
85. Kim AC, Reuter AL, Zubair M, Else T, Serecky K, Bingham NC, Lavery GG, Parker KL, Hammer GD: Targeted disruption of b-catenin in Sf1-expressing cells impairs development and maintenance of the adrenal cortex. Development 135:2593-2602, 2008
86. Kirschner LS: Signaling pathways in adrenocortical cancer. Ann N Y Acad Sci 968:222-239, 2002
87. Kirschner LS: Emerging treatment strategies for adrenocortical carcinoma: a new hope. J Clin Endocrinol Metab 91:14-21, 2006
88. Kjellman M, Kallioniemi OP, Karhu R, Hoog A, Farnebo LO, Auer G, Larsson C, Backdahl M: Genetic aberrations in adrenocortical tumors detected using comparative genomic hybridization correlate with tumor size and malignancy. Cancer Res 56:4219-4223, 1996
89. Kjellman M, Larsson C, Backdahl M: Genetic background of adrenocortical tumor development. World J Surg 25:948-956, 2001
90. Kjellman M, Roshani L, Teh BT, Kallioniemi OP, Hoog A, Gray S, Farnebo LO, Holst M, Backdahl M, Larsson C: Genotyping of adrenocortical tumors: very frequent deletions of the MEN1 locus in 11q13 and of a 1-centimorgan region in 2p16. J Clin Endocrinol Metab 84:730-735, 1999
91. Kleihues P, SchaubleB, zur HA, Esteve J, Ohgaki H: Tumors associated with p53 germline mutations: a synopsis of 91 families. Am J Pathol 150:1-13, 1997
92. Koch CA, Pacak K, Chrousos GP: The molecular pathogenesis of hereditary and sporadic adreno-cortical and adrenomedullary tumors. J Clin En-docrinol Metab 87:5367-5384, 2002
93. Kumar TR, Donehower LA, Bradley A, Matzuk MM: Transgenic mouse models for tumour-suppressor genes. J Intern Med 238:233-238, 1995
94. Lacroix A, Bourdeau I: Bilateral adrenal Cushing's syndrome: macronodular adrenal hyperplasia and primary pigmented nodular adrenocortical disease. Endocrinol Metab Clin North Am 34:441-458, x, 2005
95. Lalli E, Melner MH, Stocco DM, Sassone-Corsi P: DAX-1 blocks steroid production at multiple levels. Endocrinology 139:4237-4243, 1998
96. Leboulleux S, Gaston V, Boulle N, Le BY, Gicquel C: Loss of heterozygosity at the mannose 6-phosphate/insulin-like growth factor 2 receptor locus: a frequent but late event in adrenocortical tumorigenesis. Eur J Endocrinol 144:163-168, 2001
97. Lehtonen HJ, Kiuru M, Ylisaukko-Oja SK, Salovaara R, Herva R, Koivisto PA, Vierimaa O, Aittomäki K, Pukkala E, Launonen V, Aaltonen LA: Increased risk of cancer in patients with fumarate hydratase germline mutation. J Med Genet 43:523-526, 2006
98. 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 29:22-32, 2008
99. Levine AJ, Feng Z, Mak TW, You H, Jin S: Coordination and communication between the p53 and IGF-1-AKT-TOR signal transduction pathways. Genes Dev 20:267-275, 2006
100. Li T, Vu TH, Ulaner GA, Littman E, Ling JQ, Chen HL, Hu JF, Behr B, Giudice L, Hoffman AR: IVF results in de novo DNA methylation and histone methylation at an Igf2-H19 imprinting epigenetic switch. Mol Hum Reprod 11:631-640, 2005
101. Libé R, Bertherat J: Molecular genetics of adrenocortical tumours, from familial to sporadic diseases. Eur J Endocrinol 153:477-487, 2005
102. Libé R, Fratticci A, Bertherat J: Adrenocortical cancer: pathophysiology and clinical management. Endocr Relat Cancer 14:13-28, 2007
103. Libé R, Groussin L, Tissier F, Elie C, Rene-Corail F, Fratticci A, Jullian E, Beck-Peccoz P, Bertagna X, Gicquel C, Bertherat J: Somatic TP53 mutations are relatively rare among adrenocortical cancers with the frequent 17p13 loss of heterozygosity. Clin Cancer Res 13:844-850, 2007
104. Lichtenauer UD, Shapiro I, Geiger K, Quinkler M, Fassnacht M, Nitschke R, Ruckauer KD, Beuschlein F: Side population does not define stem celllike cancer cells in the adrenocortical carcinoma cell line NCI h295R. Endocrinology 149:1314-1322, 2008
105. Lin Y, Liu A, Zhang S, Ruusunen T, Kreidberg JA, Peltoketo H, Drummond I, Vainio S: Induction of ureter branching as a response to Wnt-2b signaling during early kidney organogenesis. Dev Dyn 222:26-39, 2001
106. Loffler KA, Biondi CA, Gartside M, Waring P, Stark M, Serewko-Auret MM, Muller HK, Hayward NK, Kay GF: Broad tumor spectrum in a mouse model of multiple endocrine neoplasia type 1. Int J Cancer 120:259-267, 2007
107. Looyenga BD, Hammer GD: Origin and identity of adrenocortical tumors in inhibin knockout mice: implications for cellular plasticity in the adrenal cortex. Mol Endocrinol 20:2848-2863, 2006
108. Mandel H, Shemer R, Borochowitz ZU, Okopnik M, Knopf C, Indelman M, Drugan A, Tiosano D, Gershoni-Baruch R, Choder M, Sprecher E: SERKAL syndrome: an autosomal-recessive disorder caused by a loss-of-function mutation in WNT4. Am J Hum Genet 82:39-47, 2008
109. Matyakhina L, Freedman RJ, Bourdeau I, Wei MH, Stergiopoulos SG, Chidakel A, Walther M, bu-Asab M, Tsokos M, Keil M, Toro J, Linehan WM, Stratakis CA: Hereditary leiomyomatosis associated with bilateral, massive, macronodular adrenocortical disease and atypical cushing syndrome: a clinical and molecular genetic investigation. J Clin Endocrinol Metab 90:3773-3779, 2005
110. Mazzuco TL, Chabre O, Feige JJ, Thomas M: Aberrant expression of human luteinizing hormone receptor by adrenocortical cells is sufficient to provoke both hyperplasia and Cushing's syndrome features. J Clin Endocrinol Metab 91:196-203, 2006
111. Mazzuco TL, Chabre O, Feige JJ, Thomas M: Aberrant GPCR expression is a sufficient genetic event to trigger adrenocortical tumorigenesis. Mol Cell Endocrinol 265-266:23-28, 2007
112. Mazzuco TL, Chabre O, Sturm N, Feige JJ, Thomas M: Ectopic expression of the gastric inhibitory polypeptide receptor gene is a sufficient genetic event to induce benign adrenocortical tumor in a xenotransplantation model. Endocrinology 147:782-790, 2006
113. Morley SD, Viard I, Chung BC, Ikeda Y, Parker KL, Mullins JJ: Variegated expression of a mouse steroid 21-hydroxylase/b-galactosidase transgene suggests centripetal migration of adrenocortical cells. Mol Endocrinol 10:585-598, 1996
114. Mould AW, Duncan R, Serewko-Auret M, Loffler KA, Biondi C, Gartside M, Kay GF, Hayward NK: Global expression profiling of murine MEN1-associated tumors reveals a regulatory role for menin in transcription, cell cycle and chromatin remodelling. Int J Cancer 121:776-783, 2007
115. Murthy AS, Russfield AB: Evidence for three types of benign adrenal tumors in Syrian hamsters. Arch Pathol 81:140-145, 1966
116. Myers NC, III: Adrenal incidentalomas. Diagnostic workup of the incidentally discovered adrenal mass. Vet Clin North Am Small Anim Pract 27:381-399, 1997
117. O'Hagan RC, Chang S, Maser RS, Mohan R, Artandi SE, Chin L, DePinho RA: Telomere dysfunction provokes regional amplification and deletion in cancer genomes. Cancer Cell 2:149-155, 2002
118. Parviainen H, Kiiveri S, Bielinska M, Rahman N, Huhtaniemi IT, Wilson DB, Heikinheimo M: GATA transcription factors in adrenal development and tumors. Mol Cell Endocrinol 265-266:17-22, 2007
119. Perrault SD, Hornsby PJ, Betts DH: Global gene expression response to telomerase in bovine adre-nocortical cells. Biochem Biophys Res Commun 335:925-936, 2005
120. Pianovski MA, Cavalli LR, Figueiredo BC, Santos SC, Doghman M, Ribeiro RC, Oliveira AG, Michalkiewicz E, Rodrigues GA, Zambetti G, Haddad BR, Lalli E: SF-1 overexpression in childhood adrenocortical tumours. Eur J Cancer 42:1040-1043, 2006
121. Pinto EM, Billerbeck AE, Fragoso MC, Mendonca BB, Latronico AC: Deletion mapping of chromosome 17 in benign and malignant adrenocortical tumors associated with the Arg337His mutation of the p53 tumor suppressor protein. J Clin Endocrinol Metab 90:2976-2981, 2005
122. Prunier C, Hocevar BA, Howe PH: Wnt signaling: physiology and pathology. Growth Fact 22:141-150, 2004
123. Quinkler M, Hahner S, Wortmann S, Johanssen S, Adam P, Ritter C, Strasburger C, Allolio B, Fassnacht M: Treatment of advanced adrenocorti-cal carcinoma with erlotinib plus gemcitabine. J Clin Endocrinol Metab 93:2057-2062, 2008
124. Rainey WE, Rehman KS, Carr BR: The human fetal adrenal: making adrenal androgens for placental estrogens. Semin Reprod Med 22:327-336, 2004
125. Ribeiro RC, Rodriguez-Galindo C, Figueiredo BC, Mastellaro MJ, West AN, Kriwacki R, Zambetti GP: Germline TP53 R337H mutation is not sufficient to establish Li-Fraumeni or Li-Fraumeni-like syndrome. Cancer Lett 247:353-355, 2007
126. Rivera RM, Stein P, Weaver JR, Mager J, Schultz RM, Bartolomei MS: Manipulations of mouse embryos prior to implantation result in aberrant expression of imprinted genes on day 9.5 of development. Hum Mol Genet 17:1-14, 2008
127. Romero DG, Rilli S, Plonczynski MW, Yanes LL, Zhou MY, Gomez-Sanchez EP, Gomez-Sanchez CE: Adrenal transcription regulatory genes modulated by angiotensin II and their role in steroidogenesis. Physiol Genomics 30:26-34, 2007
128. Schulte DM, Shapiro I, Reincke M, Beuschlein F: Expression and spatio-temporal distribution of differentiation and proliferation markers during mouse adrenal development. Gene Expr Patterns 7:72-81, 2007
129. Schulte KM, Mengel M, Heinze M, Simon D, Scheuring S, Kohrer K, Roher HD: Complete sequencing and messenger ribonucleic acid expression analysis of the MEN I gene in adrenal cancer. J Clin Endocrinol Metab 85:441-448, 2000
130. Shi Y, Massague J: Mechanisms of TGF-b signaling from cell membrane to the nucleus. Cell 113:685-700, 2003
131. Sidhu S, Marsh DJ, Theodosopoulos G, Philips J, Bambach CP, Campbell P, Magarey CJ, Russell CF, Schulte KM, Roher HD, Delbridge L, Robinson BG: Comparative genomic hybridization analysis of adrenocortical tumors. J Clin Endocrinol Metab 87:3467-3474, 2002
132. Simone-Freilicher E: Adrenal gland disease in ferrets. Vet Clin North Am Exot Anim Pract 11:125-137, 2008
133. Sinclair KD, Young LE, Wilmut I, McEvoy TG: In-utero overgrowth in ruminants following em-bryo culture: lessons from mice and a warning to men. Hum Reprod 15(Suppl 5):68-86, 2000
134. Soon PS, Libe R, Benn DE, Gill A, Shaw J, Sywak MS, Groussin L, Bertagna X, Gicquel C, Bertherat J, McDonald KL, Sidhu SB, Robinson BG: Loss of heterozygosity of 17p13, with possible involvement of ACADVL and ALOX15B, in the pathogenesis of adrenocortical tumors. Ann Surg 247:157-164, 2008
135. Soussi T, Wiman KG: Shaping genetic alterations in human cancer: the p53 mutation paradigm. Cancer Cell 12:303-312, 2007
136. Stratakis CA: Adrenocortical tumors, primary pigmented adrenocortical disease (PPNAD)/Carney complex, and other bilateral hyperplasias: the NIH studies. Horm Metab Res 39:467-473, 2007
137. Sun B, Huang Q, Liu S, Chen M, Hawks CL, Wang L, Zhang C, Hornsby PJ: Progressive loss of malignant behavior in telomerase-negative tumorigenic adrenocortical cells and restoration of tumorigenicity by human telomerase reverse tran-scriptase. Cancer Res 64:6144-6151, 2004
138. Swords FM, Baig A, Malchoff DM, Malchoff CD, Thorner MO, King PJ, Hunyady L, Clark AJ: Impaired desensitization of a mutant adrenocorticotropin receptor associated with apparent constitutive activity. Mol Endocrinol 16:2746-2753, 2002
139. Tadjine M, Lampron A, Ouadi L, Bourdeau I: Frequent mutations of beta-catenin gene in sporadic secreting adrenocortical adenomas. Clin Endocrinol (Oxf) 68:264-270, 2008
140. Tadjine M, Lampron A, Ouadi L, Horvath A, Stratakis CA, Bourdeau I: Detection of somatic beta-catenin mutations in primary pigmented nodular adrenocortical disease. Clin Endocrinol (Oxf) 69:367-373, 2008
141. Tetsu O, McCormick F: Beta-catenin regulates expression of cyclin D1 in colon carcinoma cells. Nature 398:422-426, 1999
142. Tissier F, Cavard C, Groussin L, Perlemoine K, Fumey G, Hagnere AM, Rene-Corail F, Jullian E, Gicquel C, Bertagna X, Vacher-Lavenu MC, Perret C, Bertherat J: Mutations of beta-catenin in adrenocortical tumors: activation of the Wnt signaling pathway is a frequent event in both benign and malignant adrenocortical tumors. Cancer Res 65:7622-7627, 2005
143. Tosh D, Slack JM: How cells change their phenotype. Nat Rev Mol Cell Biol 3:187-194, 2002
144. Val P, Martinez-Barbera JP, Swain A: Adrenal development is initiated by Cited2 and Wt1 through modulation of Sf-1 dosage. Development 134:2349-2358, 2007
145. van Nederveen FH, de Krijger RR: Precursor lesions of the adrenal gland. Pathobiology 74:285-290, 2007
146. Vanttinen T, Liu J, Kuulasmaa T, Kivinen P, Voutilainen R: Expression of activin/inhibin signaling components in the human adrenal gland and the effects of activins and inhibins on adrenocortical steroidogenesis and apoptosis. J Endocrinol 178:479-489, 2003
147. Venteicher AS, Meng Z, Mason PJ, Veenstra TD, Artandi SE: Identification of ATPases pontin and reptin as telomerase components essential for holoenzyme assembly. Cell 132:945-957, 2008
148. Verdun RE, Karlseder J: Replication and protection of telomeres. Nature 447:924-931, 2007
149. Viger RS, Guittot SM, Anttonen M, Wilson DB, Heikinheimo M: Role of the GATA family of transcription factors in endocrine development, function, and disease. Mol Endocrinol 22:781-798, 2008
150. Volante M, Buttigliero C, Greco E, Berruti A, Papotti M: Pathological and molecular features of adrenocortical carcinoma: an update. J Clin Pathol 61:787-793, 2008
151. Vucic EA, Brown CJ, Lam WL: Epigenetics of cancer progression. Pharmacogenomics 9:215-234, 2008
152. Vuorenoja S, Rivero-Muller A, Kiiveri S, Bielinska M, Heikinheimo M, Wilson DB, Huhtaniemi IT, Rahman NA: Adrenocortical tumorigenesis, luteinizing hormone receptor and transcription factors GATA-4 and GATA-6. Mol Cell Endocrinol 269:38-45, 2007
153. Wagner S, Kiupel M, Peterson RA, Heikinheimo M, Wilson DB: Cytochrome b5 expression in gonadectomy-induced adrenocortical neoplasms of the domestic ferret (Mustela putorius furo). Vet Pathol 45:439-442, 2008
154. Weber MM, Auernhammer CJ, Kiess W, Engel-hardt D: Insulin-like growth factor receptors in normal and tumorous adult human adrenocortical glands. Eur J Endocrinol 136:296-303, 1997
155. Weber MM, Fottner C, Wolf E: The role of the insulin-like growth factor system in adrenocortical tumourigenesis. Eur J Clin Invest 30(Suppl 3): 69-75, 2000
156. West AN, Neale GA, Pounds S, Figueredo BC, Rodriguez GC, Pianovski MA, Oliveira Filho AG, Malkin D, Lalli E, Ribeiro R, Zambetti GP: Gene expression profiling of childhood adrenocortical tumors. Cancer Res 67:600-608, 2007
157. Wright BJ, Conner GH: Adrenal neoplasms in slaughtered cattle. Cancer Res 28:251-263, 1968
158. Young KM, Walker SL, Lanthier C, Waddell WT, Monfort SL, Brown JL: Noninvasive monitoring of adrenocortical activity in carnivores by fecal glucocorticoid analyses. Gen Comp Endocrinol 137:148-165, 2004
159. Young LE, Fernandes K, McEvoy TG, Butterwith SC, Gutierrez CG, Carolan C, Broadbent PJ, Robinson JJ, Wilmut I, Sinclair KD: Epigenetic change in IGF2R is associated with fetal overgrowth after sheep embryo culture. Nat Genet 27: 153-154, 2001
160. Young LE, Sinclair KD, Wilmut I: Large offspring syndrome in cattle and sheep. Rev Reprod 3:155-163, 1998
161. Zambetti GP: The p53 mutation "gradient effect" and its clinical implications. J Cell Physiol 213: 370-373, 2007
162. Zazopoulos E, Lalli E, Stocco DM, Sassone-Corsi P: DNA binding and transcriptional repression by DAX-1 blocks steroidogenesis. Nature 390:311-315, 1997
163. Zhao J, Speel EJ, Muletta-Feurer S, Rutimann K, Saremaslani P, Roth J, Heitz PU, Komminoth P: Analysis of genomic alterations in sporadic adrenocortical lesions. Gain of chromosome 17 is an early event in adrenocortical tumorigenesis. Am J Pathol 155:1039-1045, 1999
164. Zhao L, Bakke M, Hanley NA, Majdic G, Stallings NR, Jeyasuria P, Parker KL: Tissue-specific knockouts of steroidogenic factor 1. Mol Cell Endocrinol 215:89-94, 2004
165. Zubair M, Ishihara S, Oka S, Okumura K, Morohashi K: Two-step regulation of Ad4BP/SF-1 gene transcription during fetal adrenal development: initiation by a Hox-Pbx1-Prep1 complex and maintenance via autoregulation by Ad4BP/SF-1. Mol Cell Biol 26:4111-4121, 2006