Advertisement

Mouse Models of Adrenal Tumorigenesis

  • Felix Beuschlein
Chapter

Abstract

Over the past decade, a number of high-throughput techniques have emerged as powerful tools for molecular and functional characterization of cancer cells. These techniques allow for genetic or epigenetic analysis of DNA, determination of RNA expression pattern, proteomic profiling, or characterization of posttranslational modification. Despite these technical advances that aid thorough molecular characterization of surgical tumor material, most of the functional properties of biological molecules are still unpredictable from pure expression and sequence analysis. For functional studies of gene products, mouse models continue to be intensively utilized as an experimental system due to the similarity to humans with respect to genome organization, development, and physiology.

Keywords

Adrenal Cortex Adrenal Tumor Gastric Inhibitory Polypeptide Inbred Mouse Strain Adrenocortical Tumor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

References

  1. 1.
    Cohen AI et al (1957) Histologic and physiologic characteristics of hormone-secreting transplantable adrenal tumors in mice and rats. Am J Pathol 33:631–651PubMedGoogle Scholar
  2. 2.
    Humphreys SR et al (1965) Transplantation characteristics and response to chemotherapy of a murine adrenal tumor. Eur J Cancer 1:125–133PubMedGoogle Scholar
  3. 3.
    Cohen AI, Furth J (1959) Corticotropin assay with transplantable adrenocortical tumor slices: application to the assay of adrenotropic pituitary tumors. Cancer Res 19:72–78PubMedGoogle Scholar
  4. 4.
    Yasumura Y et al (1966) Clonal analysis of differentiated function in animal cell cultures. I. Possible correlated maintenance of differentiated function and the diploid karyotype. Cancer Res 26:529–535PubMedGoogle Scholar
  5. 5.
    Rainey WE et al (2004) Adrenocortical cell lines. Mol Cell Endocrinol 228:23–38PubMedCrossRefGoogle Scholar
  6. 6.
    Woolley GW, Little CC (1945) The incidence of adrenal cortical carcinoma in gonadectomized female mice of the extreme dilution strain. I Observation on the adrenal cortex. Cancer Res 5:193–202Google Scholar
  7. 7.
    Johnsen IK et al (2006) Gonadectomy in mice of the inbred strain CE/J induces proliferation of sub-capsular adrenal cells expressing gonadal marker genes. J Endocrinol 190:47–57PubMedCrossRefGoogle Scholar
  8. 8.
    Bielinska M et al (2003) Mouse strain susceptibility to gonadectomy-induced adrenocortical tumor formation correlates with the expression of GATA-4 and luteinizing hormone receptor. Endocrinology 144:4123–4133.PubMedCrossRefGoogle Scholar
  9. 9.
    Murthy AS et al (1970) Postcastrational adrenal tumors in two strains of mice: morphologic, histochemical, and chromatographic studies. J Natl Cancer Inst 45:1211–1222PubMedGoogle Scholar
  10. 10.
    Bielinska M et al (2005) Gonadotropin-induced adrenocortical neoplasia in NU/J nude mice. Endocrinology 146:3975–3984PubMedCrossRefGoogle Scholar
  11. 11.
    Russfield AB (1975) Experimental endocrinopathies. Methods Achiev Exp Pathol 7:132–148PubMedGoogle Scholar
  12. 12.
    Woolley GW, Little CC (1946) Transplantation of an adrenal cortical carcinoma. Cancer Res 6:712–717PubMedGoogle Scholar
  13. 13.
    Woolley GW, Little CC (1945) The incidence of adrenal cortical carcinoma in gonadectomized female mice of the extreme dilution strain. II. Observation on the accessory sex organs. Cancer Res 5:203–210Google Scholar
  14. 14.
    Tremblay JJ, Viger RS (2001) GATA factors differentially activate multiple gonadal promoters through conserved GATA regulatory elements. Endocrinology 142:977–986PubMedCrossRefGoogle Scholar
  15. 15.
    Laitinen MP et al (2000) Transcription factors GATA-4 and GATA-6 and a GATA family cofactor, FOG-2, are expressed in human ovary and sex cord-derived ovarian tumors. J Clin Endocrinol Metab 85:3476–3483PubMedCrossRefGoogle Scholar
  16. 16.
    Looyenga BD, Hammer GD (2006) Origin and identity of adrenocortical tumors in inhibin knockout mice: implications for cellular plasticity in the adrenal cortex. Mol Endocrinol 20:2848–2863PubMedCrossRefGoogle Scholar
  17. 17.
    Bernichtein S et al (2008) Adrenal gland tumorigenesis after gonadectomy in mice is a complex genetic trait driven by epistatic loci. Endocrinology 149:651–661PubMedCrossRefGoogle Scholar
  18. 18.
    Luo X et al (1994) A cell-specific nuclear receptor is essential for adrenal and gonadal development and sexual differentiation. Cell 77:481–490PubMedCrossRefGoogle Scholar
  19. 19.
    Frigeri C et al (2002) A polymorphic form of steroidogenic factor-1 is associated with adrenocorticotropin resistance in y1 mouse adrenocortical tumor cell mutants. Endocrinology 143:4031–4037PubMedCrossRefGoogle Scholar
  20. 20.
    Figueiredo BC et al (2005) Amplification of the steroidogenic factor 1 gene in childhood adrenocortical tumors. J Clin Endocrinol Metab 90:615–619PubMedCrossRefGoogle Scholar
  21. 21.
    Doghman M et al (2007) Increased steroidogenic factor-1 dosage triggers adrenocortical cell proliferation and cancer. Mol Endocrinol 21:2968–2987PubMedCrossRefGoogle Scholar
  22. 22.
    Kim AC et al (2009) In search of adrenocortical stem and progenitor cells. Endocr Rev 30:241–263PubMedCrossRefGoogle Scholar
  23. 23.
    Yamazaki H et al (1998) Establishment of an adrenocortical carcinoma xenograft with normotensive hyperaldosteronism in vivo. Apmis 106:1056–1060PubMedCrossRefGoogle Scholar
  24. 24.
    Logie A et al (2000) Establishment and characterization of a human adrenocortical carcinoma xenograft model. Endocrinology 141:3165–3171PubMedCrossRefGoogle Scholar
  25. 25.
    Gazdar AF et al (1990) Establishment and characterization of a human adrenocortical carcinoma cell line that expresses multiple pathways of steroid biosynthesis. Cancer Res 50:5488–5496PubMedGoogle Scholar
  26. 26.
    Leibovitz A et al (1973) New human cancer cell culture lines. I. SW-13, small-cell carcinoma of the adrenal cortex. J Natl Cancer Inst 51:691–697PubMedGoogle Scholar
  27. 27.
    Schteingart DE et al (2001) Overexpression of CXC chemokines by an adrenocortical carcinoma: a novel clinical syndrome. J Clin Endocrinol Metab 86:3968–3974PubMedCrossRefGoogle Scholar
  28. 28.
    Barlaskar FM et al (2009) Preclinical targeting of the type I insulin-like growth factor receptor in adrenocortical carcinoma. J Clin Endocrinol Metab 94:204–212PubMedCrossRefGoogle Scholar
  29. 29.
    Wolkersdorfer GW et al (2002) A novel approach using transcomplementing adenoviral vectors for gene therapy of adrenocortical cancerACC. Horm Metab Res 34:279–287PubMedCrossRefGoogle Scholar
  30. 30.
    Zwermann O et al (2005) ACTH 1-24 inhibits proliferation of adrenocortical tumors in vivo. Eur J Endocrinol 153:435–444PubMedCrossRefGoogle Scholar
  31. 31.
    Reincke M et al (1997) Deletion of the adrenocorticotropin receptor gene in human adrenocortical tumors: implications for tumorigenesis. J Clin Endocrinol Metab 82:3054–3058PubMedCrossRefGoogle Scholar
  32. 32.
    Hornsby PJ (2001) Transplantation of adrenocortical cells. Rev Endocr Metab Disord 2:313–321PubMedCrossRefGoogle Scholar
  33. 33.
    Thomas M et al (2003) Adrenocortical cell transplantation in scid mice: the role of the host animals’ adrenal glands. J Steroid Biochem Mol Biol 85:285–290PubMedCrossRefGoogle Scholar
  34. 34.
    Thomas M et al (2000) Formation of functional tissue from transplanted adrenocortical cells expressing telomerase reverse transcriptase. Nat Biotechnol 18: 39–42PubMedCrossRefGoogle Scholar
  35. 35.
    Thomas M et al (2002) Cooperation of TERT, SV40 T antigen and oncogenic Ras in tumorigenesis: a cell transplantation model using bovine adrenocortical cells. Neoplasia 4:493–500PubMedCrossRefGoogle Scholar
  36. 36.
    Sun B et al (2004) Progressive loss of malignant behavior in telomerase-negative tumorigenic adrenocortical cells and restoration of tumorigenicity by human telomerase reverse transcriptase. Cancer Res 64:6144–6151PubMedCrossRefGoogle Scholar
  37. 37.
    Lacroix A et al (2004) Cushing’s syndrome variants secondary to aberrant hormone receptors. Trends Endocrinol Metab 15:375–382PubMedGoogle Scholar
  38. 38.
    Mazzuco TL et al (2006) Ectopic expression of the gastric inhibitory polypeptide receptor gene is a sufficient genetic event to induce benign adrenocortical tumor in a xenotransplantation model. Endocrinology 147:782–790PubMedCrossRefGoogle Scholar
  39. 39.
    Mazzuco TL et al (2006) 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 91:196–203PubMedCrossRefGoogle Scholar
  40. 40.
    Ortmann D et al (2004) Steroidogenic acute regulatory (StAR)-directed immunotherapy protects against tumor growth of StAR-expressing Sp2-0 cells in a rodent adrenocortical carcinoma model. Endocrinology 145:1760–1766PubMedCrossRefGoogle Scholar
  41. 41.
    Giordano TJ et al (2003) Distinct transcriptional profiles of adrenocortical tumors uncovered by DNA microarray analysis. Am J Pathol 162:521–531PubMedGoogle Scholar
  42. 42.
    Weber MM et al (1997) Insulin-like growth factor receptors in normal and tumorous adult human adrenocortical glands. Eur J Endocrinol 136:296–303PubMedCrossRefGoogle Scholar
  43. 43.
    Compagnone NA et al (1997) Characterization of adrenocortical cell lines produced by genetically targeted tumorigenesis in transgenic mice. Steroids 62:238–243PubMedCrossRefGoogle Scholar
  44. 44.
    Sahut-Barnola I et al (2000) Adrenal tumorigenesis targeted by the corticotropin-regulated promoter of the aldo-keto reductase AKR1B7 gene in transgenic mice. Endocr Res 26:885–898PubMedCrossRefGoogle Scholar
  45. 45.
    Kananen K et al (1996) Gonadectomy permits adrenocortical tumorigenesis in mice transgenic for the mouse inhibin alpha-subunit promoter/simian virus 40 T-antigen fusion gene: evidence for negative autoregulation of the inhibin alpha- subunit gene. Mol Endocrinol 10:1667–1677PubMedCrossRefGoogle Scholar
  46. 46.
    Ragazzon B et al (2006) Adrenocorticotropin-dependent changes in SF-1/DAX-1 ratio influence steroidogenic genes expression in a novel model of glucocorticoid-producing adrenocortical cell lines derived from targeted tumorigenesis. Endocrinology 147:1805–1818PubMedCrossRefGoogle Scholar
  47. 47.
    Kananen K et al (1995) Gonadal tumorigenesis in transgenic mice bearing the mouse inhibin alpha-subunit promoter/simian virus T-antigen fusion gene: characterization of ovarian tumors and establishment of gonadotropin-responsive granulosa cell lines. Mol Endocrinol 9:616–627PubMedCrossRefGoogle Scholar
  48. 48.
    Roberts VJ et al (1991) Expression of inhibin/activin subunit messenger ribonucleic acids during rat embryogenesis. Endocrinology 128:3122–3129PubMedCrossRefGoogle Scholar
  49. 49.
    Kananen K et al (1997) Suppression of gonadotropins inhibits gonadal tumorigenesis in mice transgenic for the mouse inhibin alpha-subunit promoter/simian virus 40 T-antigen fusion gene. Endocrinology 138:3521–3531PubMedCrossRefGoogle Scholar
  50. 50.
    Rilianawati et al (1998) Direct luteinizing hormone action triggers adrenocortical tumorigenesis in castrated mice transgenic for the murine inhibin alpha-subunit promoter/simian virus 40 T-antigen fusion gene. Mol Endocrinol 12:801–809PubMedCrossRefGoogle Scholar
  51. 51.
    Rilianawati et al (2000) Long-term testosterone treatment prevents gonadal and adrenal tumorigenesis of mice transgenic for the mouse inhibin-alpha subunit promoter/simian virus 40 T-antigen fusion gene. J Endocrinol 166:77–85PubMedCrossRefGoogle Scholar
  52. 52.
    Rahman NA et al (2004) Adrenocortical tumorigenesis in transgenic mice expressing the inhibin alpha-subunit promoter/simian virus 40 T-antigen transgene: relationship between ectopic expression of luteinizing hormone receptor and transcription factor GATA-4. Mol Endocrinol 18:2553–2569PubMedCrossRefGoogle Scholar
  53. 53.
    Mikola M et al (2003) High levels of luteinizing hormone analog stimulate gonadal and adrenal tumorigenesis in mice transgenic for the mouse inhibin-alpha-subunit promoter/Simian virus 40 T-antigen fusion gene. Oncogene 22:3269–3278PubMedCrossRefGoogle Scholar
  54. 54.
    Vuorenoja S et al (2007) Adrenocortical tumorigenesis, luteinizing hormone receptor and transcription factors GATA-4 and GATA-6. Mol Cell Endocrinol 269:38–45PubMedCrossRefGoogle Scholar
  55. 55.
    Vuorenoja S et al (2008) Targeted therapy for adrenocortical tumors in transgenic mice through their LH receptor by Hecate-human chorionic gonadotropin beta conjugate. Endocr Relat Cancer 15:635–648PubMedCrossRefGoogle Scholar
  56. 56.
    Vuorenoja S et al (2009) Hecate-CG{beta} conjugate and gonadotropin suppression shows two distinct mechanisms of action in the treatment of adrenocortical tumors in transgenic mice expressing Simian Virus 40 T antigen under inhibin-{alpha} promoter. Endocr Relat Cancer 16:549–564PubMedCrossRefGoogle Scholar
  57. 57.
    Doghman M et al (2009) Inhibition of adrenocortical carcinoma cell proliferation by steroidogenic factor-1 inverse agonists. J Clin Endocrinol Metab 94:2178–2183PubMedCrossRefGoogle Scholar
  58. 58.
    Matzuk MM et al (1992) Alpha-inhibin is a tumour-suppressor gene with gonadal specificity in mice. Nature 360:313–319PubMedCrossRefGoogle Scholar
  59. 59.
    Beuschlein F et al (2003) Activin Induces x-Zone Apoptosis That Inhibits Luteinizing Hormone-Dependent Adrenocortical Tumor Formation in Inhibin-Deficient Mice. Mol Cell Biol 23:3951–3964.PubMedCrossRefGoogle Scholar
  60. 60.
    Matzuk MM et al (1994) Development of cancer cachexia-like syndrome and adrenal tumors in inhibin-deficient mice. Proc Natl Acad Sci U S A 91:8817–8821PubMedCrossRefGoogle Scholar
  61. 61.
    Looyenga BD, Hammer GD (2007) Genetic removal of Smad3 from inhibin-null mice attenuates tumor progression by uncoupling extracellular mitogenic signals from the cell cycle machinery. Mol Endocrinol 21:2440–2457PubMedCrossRefGoogle Scholar
  62. 62.
    Burns KH et al (2003) Cyclin D2 and p27 are tissue-specific regulators of tumorigenesis in inhibin alpha knockout mice. Mol Endocrinol 17:2053–2069PubMedCrossRefGoogle Scholar
  63. 63.
    West AN et al (2006) Identification of a novel germ line variant hotspot mutant p53-R175L in pediatric adrenal cortical carcinoma. Cancer Res 66:5056–5062PubMedCrossRefGoogle Scholar
  64. 64.
    Chari NS et al (2009) The p53 tumor suppressor network in cancer and the therapeutic modulation of cell death. Apoptosis 14:336–347PubMedCrossRefGoogle Scholar
  65. 65.
    Else T et al (2009) Genetic p53 deficiency partially rescues the adrenocortical dysplasia phenotype at the expense of increased tumorigenesis. Cancer Cell 15:465–476PubMedCrossRefGoogle Scholar
  66. 66.
    Skogseid B et al (1992) Clinical and genetic features of adrenocortical lesions in multiple endocrine neoplasia type 1. J Clin Endocrinol Metab 75:76–81PubMedCrossRefGoogle Scholar
  67. 67.
    Crabtree JS et al (2001) A mouse model of multiple endocrine neoplasia, type 1, develops multiple endocrine tumors. Proc Natl Acad Sci U S A 98:1118–1123PubMedCrossRefGoogle Scholar
  68. 68.
    Bertolino P et al (2003) Heterozygous Men1 mutant mice develop a range of endocrine tumors mimicking multiple endocrine neoplasia type 1. Mol Endocrinol 17:1880–1892PubMedCrossRefGoogle Scholar
  69. 69.
    Loffler KA et al (2007) Broad tumor spectrum in a mouse model of multiple endocrine neoplasia type 1. Int J Cancer 120:259–267PubMedCrossRefGoogle Scholar
  70. 70.
    Lichtenauer UD et al (2007) Pre-B-cell transcription factor 1 and steroidogenic factor 1 synergistically regulate adrenocortical growth and steroidogenesis. Endocrinology 148:693–704PubMedCrossRefGoogle Scholar
  71. 71.
    Kim AC et al (2008) Targeted disruption of beta-catenin in Sf1-expressing cells impairs development and maintenance of the adrenal cortex. Development 135:2593–2602PubMedCrossRefGoogle Scholar
  72. 72.
    Bose J et al (2002) Pallister-Hall syndrome phenotype in mice mutant for Gli3. Hum Mol Genet 11:1129–1135PubMedCrossRefGoogle Scholar
  73. 73.
    Cardoso CC et al (2009) New methods for investigating experimental human adrenal tumorigenesis. Mol Cell Endocrinol 300:175–179PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2009

Authors and Affiliations

  1. 1.Department of MedicineEndocrine Research, University Hospital InnenstadtMunichGermany

Personalised recommendations