Skip to main content
SpringerLink
Log in

Ret Activation in Medullary Carcinomas

  • Chapter
Molecular Basis of Thyroid Cancer

Part of the book series: Cancer Treatment and Research ((CTAR,volume 122))

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Acton D.S., Velthuyzen D., Lips C.J., Hoppener J.W. Multiple endocrine neoplasia type 2B mutation in human RET oncogene induces medullary thyroid carcinoma in transgenic mice. Oncogene 2000; 19:3121–3125.

    Article  CAS  PubMed  Google Scholar 

  2. Airaksinen M.S., Saarma M. The GDNF family: signalling, biological functions and therapeutic value. Nat Rev Neurosci 2002; 3:383–394.

    Article  CAS  PubMed  Google Scholar 

  3. Alberti L., Borrello M.G., Ghizzoni S., Torriti F., Rizzetti M.G., Pierotti M.A. GRB2 binding to the different isoforms of RET tyrosine kinase. Oncogene 1998; 17:1079–1087.

    Article  CAS  PubMed  Google Scholar 

  4. Amiel J., Lyonnet S. Hirschsprung disease, associated syndromes, and genetics: a review. J Med Genet 2001; 38:729–739.

    CAS  PubMed  Google Scholar 

  5. Anders J., Kjar S., Ibanez C.F. Molecular modeling of the extracellular domain of the RET receptor tyrosine kinase reveals multiple cadherin-like domains and a calcium-binding site. J Biol Chem 2001

    Google Scholar 

  6. Andreozzi F., Melillo R.M., Carlomagno F., Oriente F., Miele C., Fiory F., Santopietro S., Castellone M.D., Beguinot F., Santoro M., Formisano P. Protein kinase Calpha activation by RET: evidence for a negative feedback mechanism controlling RET tyrosine kinase. Oncogene 2003; 22:2942–2949.

    Article  CAS  PubMed  Google Scholar 

  7. Arighi E., Alberti L., Torriti F., Ghizzoni S., Rizzetti M.G., Pelicci G., Pasini B., Bongarzone I., Piutti C., Pierotti M.A., Borrello M.G. Identification of SHC docking site on Ret tyrosine kinase. Oncogene 1997; 14:773–782.

    Article  CAS  PubMed  Google Scholar 

  8. Asai N., Iwashita T., Matsuyama M., Takahashi M. Mechanism of activation of the ret proto-oncogene by multiple endocrine neoplasia 2A mutations. Mol Cell Biol 1995; 15, No. 3:1613–1619.

    CAS  PubMed  Google Scholar 

  9. Attie T., Pelet A., Edery P., Eng C., Mulligan L.M., Amiel J., Boutrand L., Beldjord C., Nihoul-Fekete C., Munnich A., et al. Diversity of RET proto-oncogene mutations in familial and sporadic Hirschsprung disease. Human Molec Genet 1995; 4:1381–1386.

    CAS  Google Scholar 

  10. Avantaggiato V., Dathan N.A., Grieco M., Fabien N., Lazzaro D., Fusco A., Simeone A., Santoro M. Developmental expression of the RET protooncogene. Cell Growth Diff 1994; 5:305–311.

    CAS  PubMed  Google Scholar 

  11. Baloh R.H., Enomoto H., Johnson E.M., Jr., Milbrandt J. The GDNF family ligands and receptors—implications for neural development. Curr Opin Neurobiol 2000; 10:103–110.

    Article  CAS  PubMed  Google Scholar 

  12. Beldjord C., Desclaux-Arramond F., Raffin-Sanson M., Corvol J.C., De Keyzer Y., Luton J.P., Plouin P.F., Bertagna X. The RET protooncogene in sporadic pheochromocytomas: frequent MEN 2-like mutations and new molecular defects. J Clin Endocrinol Metab 1995; 80:2063–2068.

    Article  CAS  PubMed  Google Scholar 

  13. Berndt I., Reuter M., Saller B. Frank-Raue K., Groth P., Grussendorf M., Raue F., Ritter M.M., Hoppner W. A new hot spot for mutations in the ret protooncogene causing familial medullary thyroid carcinoma and multiple endocrine neoplasia type 2A. J Clin Endocrinol Metab 1998; 83:770–774.

    Article  CAS  PubMed  Google Scholar 

  14. Besset V., Scott R.P., Ibanez C.F. Signaling complexes and protein-protein interactions involved in the activation of the Ras and P13K pathways by the c-Ret receptor tyrosine kinase. J Biol Chem 2000; 275:39159–39166.

    Article  CAS  PubMed  Google Scholar 

  15. Bolino A., Schuffenecker I., Luo Y., Seri M., Silengo M., Tocco T., Chabrier G., Houdent C., Murat A., Schlumberger M., Tourniaire J., Lenoir G.M., Omeo G. RET mutations in exons 13 and 14 of FMTC patients. Oncogene 1995; 10:2415–2419.

    CAS  PubMed  Google Scholar 

  16. Bongarzone I., Vigano’ E., Alberti L., Borrello M.G., Pasini B., Greco A., Mondellini P., Smith D.P., Ponder B.A.J., Romeo G., Pierotti M.A. Full activation of MEN2B mutant RET by an additional MEN2A mutation or by ligand (GDNF) stimulation. Oncogene 1998; 16:2295–2301.

    Article  CAS  PubMed  Google Scholar 

  17. Borrello M.G., Smith D.P., Pasini B., Bongarzone I., Greco A., Lorenzo M.J., Arighi E., Miranda C., Eng C., Alberti L., Bocciardi R., Mondellini P., Scopsi L., Romeo G., Ponder B.A.J., Pierotti M.A. RET activation by germline MEN2A and MEN2B mutations. Oncogene 1995; 11:2419–2427.

    CAS  PubMed  Google Scholar 

  18. Borrello M.G., Alberti L., Arighi E., Bongarzone I., Battistini C., Bardelli A., Pasini B., Piutti C., Rizzetti M.G., Mondellini P., Radice M.T., Pierotti M.A. The full oncogenic activity of Ret/ptc2 depends on tyrosine 539, a docking site for phospholipase Cgamma. Mol Cell Biol 1996; 16, No. 5:2151–2163.

    CAS  PubMed  Google Scholar 

  19. Borrello M.G., Mercalli E., Perego C., Degl’Innocenti D., Ghizzoni S., Arighi E., Eroini B., Rizzetti M.G., Pierotti M.A. Differential interaction of Enigma protein with the two RET isoforms. Biochem Biophys Res Commun 2002; 296:515–522.

    Article  CAS  PubMed  Google Scholar 

  20. Borst M.J., VanCamp J.M., Peacock M.L., Decker R.A. Mutational analysis of multiple endocrine neoplasia type 2A associated with Hirschsprung’s disease. Surgery 1995; 117:386–391.

    CAS  PubMed  Google Scholar 

  21. Brandi M.L., Gagel R.F., Angeli A., Bilezikian J.P., Beck-Peccoz P., Bordi C., Conte-Devolx B., Falchetti A., Gheri R.G., Libroia A., Lips C.J., Lombardi G., Mannelli M., Pacini F., Ponder B.A., Raue F., Skogseid B., Tamburrano G., Thakker R.V., Thompson N.W., Tomassetti P., Tonelli F., Wells S.A., Jr., Marx S.J. Guidelines for diagnosis and therapy of MEN type 1 and type 2. J Clin Endocrinol Metab 2001; 86:5658–5671.

    Article  CAS  PubMed  Google Scholar 

  22. Brauckhoff M., Gimm O., Hinze R., Ukkat J., Brauckhoff K., Dralle H. Papillary Thyroid Carcinoma in Patients with RET Proto-Oncogene Germline Mutation. Thyroid 2002; 12:557–561.

    Article  CAS  PubMed  Google Scholar 

  23. Brown D.A., London E. Functions of lipid rafts in biological membranes. Annu Rev Cell Dev Biol 1998; 14:111–36.: 111–136.

    Article  CAS  PubMed  Google Scholar 

  24. Cacalano G., Farinas I., Wang L., Hagler K., Forgie A., Moore M., Armanini M., Phillips H., Ryan A.M., Reichardt L., et al. GFRa1 is an essential receptor component for GDNF in the developing nervous system and kidney. Neuron 1998; 21:53–62.

    Article  CAS  PubMed  Google Scholar 

  25. Carlomagno F., Salvatore G., Cirafici A.M., De Vita G., Melillo R.M., de, Franciscis V., Billaud M., Fusco A., Santoro M. The different RET-activating capability of mutations of cysteine 620 or cysteine 634 correlates with the multiple endocrine neoplasia type 2 disease phenotype. Cancer Res 1997; 57:391–395.

    CAS  PubMed  Google Scholar 

  26. Carlomagno F., Vitagliano D., Guida T., Napolitano M., Vecchio G., Fusco A., Gazit A., Levitzki A., Santoro M. The kinase inhibitor PP1 blocks tumorigenesis induced by RET oncogenes. Cancer Res 2002; 62:1077–1082.

    CAS  PubMed  Google Scholar 

  27. Carlson K.M., Dou S., Chi D., Scavarda N.J., Toshima K., Jackson C.E., Wells S.A. Jr., Goodfellow P., Donis-Keller H. Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B. Proc Natl Acad Sci USA 1994;91:1579–1583.

    CAS  PubMed  Google Scholar 

  28. Carniti C., Perego C., Mondellini P., Pierotti M.A., Bongarzone I. PP1 inhibitor induces degradation of RETMEN2A and RETMEN2B oncoproteins through proteosomal targeting. Cancer Res 2003; 63:2234–2243.

    CAS  PubMed  Google Scholar 

  29. Carter M.T., Yome J.L., Marcil M.N., Martin C.A., Vanhorne J.B., Mulligan L.M. Conservation of RET proto-oncogene splicing variants and implications for RET isoform function. Cytogenet Cell Genet 2001; 95:169–176.

    Article  CAS  PubMed  Google Scholar 

  30. Cerchia L., Libri D., Carlomagno M.S., de F., V. The soluble ectodomain of RetC634Y inhibits both the wild-type and the constitutively active Ret. Biochem J 2003; 372:897–903

    Article  CAS  PubMed  Google Scholar 

  31. Chappuis-Flament S., Pasini A., De Vita G., Segouffin-Cariou C., Fusco A., Attie T., Lenoir G.M., Santoro M., Billaud M. Dual effect on the RET receptor of MEN 2 mutations effecting specific extracytoplasmic cysteines. Oncogene 1998; 17:2851–2861.

    Article  CAS  PubMed  Google Scholar 

  32. Chong G.C., Beahrs H., Sizemore G.W., Woolner L.H. Medullary carcinoma of the thyroid gland. Cancer 1975; 35:695–704.

    CAS  PubMed  Google Scholar 

  33. Cohen M.S., Hussain H.B., Moley J.F. Inhibition of medullary thyroid carcinoma cell proliferation and RET phosphorylation by tyrosine kinase inhibitors. Surgery 2002; 132:960–966.

    Article  PubMed  Google Scholar 

  34. Coulpier M., Anders J., Ibanez C.F. Coordinated activation of autophosphorylation sites in the RET receptor tyrosine kinase: importance of tyrosine 1062 for GDNF mediated neuronal differentiation and survival. J Biol Chem 2002; 277:1991–1999.

    Article  CAS  PubMed  Google Scholar 

  35. Dancey J.E., Schoenfeldt M. Clinical trials referral resource. Epidermal growth factor receptor inhibitors in clinical trials. Oncology (Huntingt) 2001; 15:748.

    CAS  Google Scholar 

  36. de Graaff E., Srinivas S., KilKenny C., D’Agati V., Mankoo B.S., Costantini F., Pachnis V. Differential activities of the RET tyrosine kinase receptor isoforms during mammalian embryogenesis. Genes Dev 2001; 15:2433–2444.

    PubMed  Google Scholar 

  37. Decker R.A., Peacock M.L., Watson P. Hirschsprung disease in MEN 2A: increased spectrum of RET exon 10 genotypes and strong genotype-phenotype correlation. Hum Mol Genet 1998; 7:129–134.

    Article  CAS  PubMed  Google Scholar 

  38. Donis-Keller H., Dou S., Chi D., Carlson K.M., Toshima K., Lairmore T.C., Howe J.R., Moley J., Goodfellow P., Wells S.A.Jr. Mutations in the RET proto-oncogene are associated with MEN 2A and FMTC. Human Molec Genet 1993; 2:851–856.

    CAS  Google Scholar 

  39. Donovan D.T., Levy M.L., Furst E.J., Alford B.R., Wheeler T., Tschen J.A., Gagel R.F. Familial cutaneous lichen amyloidosis in association with multiple endocrine neoplasia type 2A: a new variant. Henry Ford Hosp Med J 1989; 37:147–150.

    CAS  PubMed  Google Scholar 

  40. Drosten M., Frilling A., Stiewe T., Putzer B.M. A new therapeutic approach in medullary thyroid cancer treatment: inhibition of oncogenic RET signaling by adenoviral vector-mediated expression of a dominant-negative RET mutant. Surgery 2002; 132:991–997.

    Article  PubMed  Google Scholar 

  41. Drosten M., Putzer B.M. Gene therapeutic approaches for medullary thyroid carcinoma treatment. J Mol Med 2003a; 81:411–419.

    Article  CAS  PubMed  Google Scholar 

  42. Drosten M., Stiewe T., Putzer B.M. Antitumor capacity of a dominant-negative RET proto-oncogene mutant in a medullary thyroid carcinoma model. Hum Gene Ther 2003b; 14:971–982.

    Article  CAS  PubMed  Google Scholar 

  43. Durbec P., Marcos-Gutierrez C.V., KilKenny C., Grigoriou M., Wartiowaara K., Suvanto P., Smith D., Ponder B., Costantini F., Saarma M., Sariola H., Pachnis V. GDNF signalling through the Ret receptor tyrosine kinase. Nature 1996; 381:789–793.

    Article  CAS  PubMed  Google Scholar 

  44. Durick K., Wu R.Y., Gill G.N., Taylor S.S. Mitogenic signaling by Ret/ptc2 requires association with enigma via a LIM domain. J Biol Chem 1996; 21:12691–12694.

    Google Scholar 

  45. Edery P., Lyonnet S., Mulligan L.M., Pelet A., Dow E., Abel L., Holder S., Nihoul-Fekete’ C., Ponder B.A.J., Munnich A. Mutations of the RET proto-oncogene in Hirschsprung’s disease. Nature 1994; 367:378–380.

    Article  CAS  PubMed  Google Scholar 

  46. Eng C., Smith D.P., Mulligan L.M., Nagai M.A., Healey C.S., Ponder M.A., Gardner E., Scheumann G.F.W., Jackson C.E., Tunnacliffe A., Ponder B.A.J. Point mutation within the tyrosine kinase domain of the RET proto-oncogene in multiple endocrine neoplasia type 2B and related sporadic tumours. Human Molec Genet 1994; 3:237–241.

    CAS  Google Scholar 

  47. Eng C., Smith D.P., Mulligan L.M., Healey C.S., Zvelebil M.J., Stonehouse T.J., Ponder M.A., Jackson C.E., Waterfield M.D., Ponder B.A.J. A novel point mutation in the Tyrosine kinase domain of the RET proto-oncogene in sporadic medullari thyroid carcinoma and in a family with FMTC. Oncogene 1995; 10:509–513.

    CAS  PubMed  Google Scholar 

  48. Eng C., Clayton D., Schuffenecker I., Lenoir G., Cote G., Gagel R.F., Van, Amstel H.K., Lips C.J., Nishisho I., Takai S.I., Marsh D.J., Robinson B.G., Fran-Raue K., Raue F., Xue F., Noll W.W., Romei C., Pacini F., Fink M., Niederle B., Zedenius J., Nordenskjold M., Komminoth P., Hendy G.N., Mulligan L.M. The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis. JAMA 1996a; 276:1575–1579.

    Article  CAS  PubMed  Google Scholar 

  49. Eng C., Mulligan L.M., Healey C.S., Houghton C., Frilling A., Raue F., Thomas G.A., Ponder B.A. Heterogeneous mutation of the RET proto-oncogene in subpopulations of medullary thyroid carcinoma. Cancer Res 1996b; 56:2167–2170.

    CAS  PubMed  Google Scholar 

  50. Eng C., RET proto-oncogene in the development of human cancer. J Clin Oncol 1999; 17:380–393.

    CAS  PubMed  Google Scholar 

  51. Farndon J.R., Leight G.S., Dilley W.G., Baylin S.B., Smallridge R.C., Harrison T.S., Wells S.A., Jr. Familial medullary thyroid carcinoma without associated endocrinopathies: a distinct clinical entity. Br J Surg 1986; 73:278–281.

    CAS  PubMed  Google Scholar 

  52. Fattoruso O., Quadro L., Libroia A., Verga U., Lupoli G., Cascone E., Colantuoni V. A GTG to ATG novel point mutation at codon 804 in exon 14 of the RET proto-oncogene in two families affected by familial medullary thyroid carcinoma. Hum Mutat 1998; Suppl 1:167–71.

    Google Scholar 

  53. Feldman G.L., Edmonds M.W., Ainsworth P.J., Schuffenecker I., Lenoir G.M., Saxe A.W., Talpos G.B., Roberson J., Petrucelli N., Jackson C.E. Variable expressivity of familial medullary thyroid carcinoma (FMTC) due to a RET V804M (GTG->ATG) mutation. Surgery 2000; 128:93–98.

    Article  CAS  PubMed  Google Scholar 

  54. Frischauf A.M. Positional cloning uncovers a new old oncogene. Hum Mol Genet 1993; 2:847–848.

    CAS  PubMed  Google Scholar 

  55. Gagel R.F., Tashjian A.H., Jr., Cummings T., Papathanasopoulos N., Kaplan M.M., Delellis R.A., Wolfe H.J., Reichlin S. The clinical outcome of prospective screening for multiple endocrine neoplasia type 2a. An 18-year experience. N Engl J Med 1988; 318:478–484.

    CAS  PubMed  Google Scholar 

  56. Goodfellow P.J., Wells S.A., Jr. RET gene and its implications for cancer. J Natl Cancer Inst 1995; 87:1515–1523.

    CAS  PubMed  Google Scholar 

  57. Grieco M., Santoro M., Berlingieri M.T., Melillo R.M., Donghi R., Bongarzone I., Pierotti M.A., Della Porta G., Fusco A., Vecchio G. PTC is a novel rearranged form of the ret proto-oncogene and is frequently detected in vivo in human thyroid papillary carcinomas. Cell 1990; 60:557–563.

    Article  CAS  PubMed  Google Scholar 

  58. Grimm J., Sachs M., Britsch S., Di Cesare S., Schwarz-Romond T., Alitalo K., Birchmeier W. Novel p62dok family members, dok-4 and dok-5, are substrates of the c-Ret receptor tyrosine kinase and mediate neuronal differentiation. J Cell Biol 2001; 154:345–354.

    Article  CAS  PubMed  Google Scholar 

  59. Hahn M., Bishop J. Expression pattern of Drosophila ret suggests a common ancestral origin between the metamorphosis precursors in insect endoderm and the vertebrate enteric neurons. Proc Natl Acad Sci U S A 2001; 98:1053–1058.

    Article  CAS  PubMed  Google Scholar 

  60. Hayashi H., Ichihara M., Iwashita T., Murakami H., Shimono Y., Kawai K., Kurokawa K., Murakumo Y., Imai T. Characterization of intracellular signals via tyrosine 1062 in RET activated by glial cell line-derived neurotrophic factor. Oncogene 2000; 14:4469–4475.

    Google Scholar 

  61. Hayashi Y., Iwashita T., Murakamai H., Kato Y., Kawai K., Kurokawa K., Tohnai I., Ueda M., Takahashi M. Activation of BMK1 via tyrosine 1062 in RET by GDNF and MEN2A mutation. Biochem Biophys Res Commun 2001; 281:682–689.

    Article  CAS  PubMed  Google Scholar 

  62. Hazard J.B. The C cells (parafollicular cells) of the thyroid gland and medullary thyroid carcinoma. A review. Am J Pathol 1977; 88:213–250.

    CAS  PubMed  Google Scholar 

  63. Hazard J.B., Hawk W.A., Crile G. Medullary (solid) carcinoma of the thyroid—a clinicopathologic entity. J Clin Endocrinol Metab 1959; 19:152–161.

    CAS  PubMed  Google Scholar 

  64. Hennige A.M., Lammers R., Arlt D., Hoppner W., Strack V., Niederfellner G., Seif F.J., Haring H., Kellerer M. Ret oncogene signal transduction via a IRS-2/PI 3-kinase/PKB and SHC/Grb-2 dependent pathway: possible implication for transforming activity in NIH3T3 cells. Mol Cell Endocrinol 2000; 167:69–76.

    Article  CAS  PubMed  Google Scholar 

  65. Hofstra R.M., Landsvater R.M., Ceccherini I., Stulp R.P., Stelwagen T., Luo Y., Pasini B., Hoppener J.W.M., Ploos van Hamstel H.K., Romeo G., Lips C.J.M., Buys C.H.C.M. A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma. Nature 1994; 367:375–376.

    Article  CAS  PubMed  Google Scholar 

  66. Hofstra R.M., Fattoruso O., Quadro L., Wu Y., Libroia A., Verga U., Colantuoni V., Buys C.H. A novel point mutation in the intracellular domain of the ret protooncogene in a family with medullary thyroid carcinoma. J Clin Endocrinol Metab 1997; 82:4176–4178.

    Article  CAS  PubMed  Google Scholar 

  67. Hoppner W., Ritter M.M. A duplication of 12 bp in the critical cysteine rich domain of the RET proto-oncogene results in a distinct phenotype of multiple endocrine neoplasia type 2A. Human Molec Genet 1997; 6:587–590.

    CAS  Google Scholar 

  68. Hoppner W., Dralle H., Brabant G. Duplication of 9 base pairs in the critical cysteine-rich domain of the RET proto-oncogene causes multiple endocrine neoplasia type 2A. Hum Mutat 1998; Suppl 1:S128–30.:S128–S130.

    Google Scholar 

  69. Huang S.C., Koch C.A., Vortmeyer A.O., Pack S.D., Lichtenauer U.D., Mannan P., Lubensky I.A., Chrousos G.P., Gagel R.F., Pacak K., Zhuang Z. Duplication of the mutant RET allele in trisomy 10 or loss of the wild-type allele in multiple endocrine neoplasia type 2-associated pheochromocytomas. Cancer Res 2000; 60:6223–6226.

    CAS  PubMed  Google Scholar 

  70. Igaz P., Patocs A., Racz K., Klein I., Varadi A., Esik O. Occurrence of pheochromocytoma in a MEN2A family with codon 609 mutation of the RET proto-oncogene. J Clin Endocrinol Metab 2002; 87:2994.

    Article  CAS  PubMed  Google Scholar 

  71. Ishizaka Y., Itoh F., Tahira T., Ikeda I., Sugimura T., Tucker J., Fertitta A., Carrano A.V., Nagao M. Human ret proto-oncogene mapped to chromosome 10q11.2. Oncogene 1989; 4:1519–1521.

    CAS  PubMed  Google Scholar 

  72. Ito S., Iwashita T., Asai N., Murakami H., Iwata Y., Sobue G., Takahashi. Biological properties of Ret with cysteine mutations correlate with multiple endocrine neoplasia type 2A, familial medullary thyroid carcinoma, and Hirschsprung’s disease phenotype. Cancer Res 1997; 57:2870–2872.

    CAS  PubMed  Google Scholar 

  73. Iwamoto T., Taniguchi M., Asai N., Ohkusu K., Nakashima I., Takahashi M. cDNA cloning of mouse ret proto-oncogene and its sequence similarity to the cadherin superfamily. Oncogene 1993; 8:1087–1091.

    CAS  PubMed  Google Scholar 

  74. Iwashita T., Asai N., Murakami H., Matsuyama M., Takahashi M. Identification of tyrosine residues that are essential for transforming activity of the RET proto-oncogene with MEN2A or MEN2B mutation. Oncogene 1996; 12:481–487.

    CAS  PubMed  Google Scholar 

  75. Iwashita T., Kato M., Murakami H., Asai N., Ishiguro Y., Ito S., Iwata Y., Kawai K., Asai M., Kurokawa K., Kajita H., Takahashi M. Biological and biochemical properties of Ret with kinase domain mutations identified in multiple endocrine neoplasia type 2B and familial medullary thyroid carcinoma. Oncogene 1999; 18:3919–3922.

    Article  CAS  PubMed  Google Scholar 

  76. Jhiang S.M. The RET proto-oncogene in human cancers. Oncogene 2000; 19:5590–5597.

    Article  CAS  PubMed  Google Scholar 

  77. Jing S., Wen D., Yu Y., Holst P.L., Luo Y., Fang M., Tamir R., Anatonio L., Hu Z., Cupples R., Louis J.-C., Hu S., Altrock B.W., Fox G.M. GDNF-induced activation of the Ret protein tyrosine kinase is mediated by GDNFR-alpha, a novel receptor for GDNF. Cell 1996; 85:1113–1124.

    Article  CAS  PubMed  Google Scholar 

  78. Kakudo K., Carney J.A., Sizemore G.W. Medullary carcinoma of thyroid. Biologic behavior of the sporadic and familial neoplasm. Cancer 1985; 55:2818–2821.

    CAS  PubMed  Google Scholar 

  79. Kalinin V.N., Amosenko F.A., Shabanov M.A., Lubchenko L.N., Hosch S.B., Garkavtseva R.F., Izbicki J.R. Three novel mutations in the RET proto-oncogene. J Mol Med 2001; 79:609–612.

    CAS  PubMed  Google Scholar 

  80. Kasprzak L., Nolet S., Gaboury L., Pavia C., Villabona C., Rivera-Fillat F., Oriola J., Foulkes W.D. Familial medullary thyroid carcinoma and prominent corneal nerves associated with the germline V804M and V778I mutations on the same allele of RET. J Med Genet 2001; 38:784–787.

    Article  CAS  PubMed  Google Scholar 

  81. Kawai K., Iwashita T., Murakami H., Hiraiwa N., Yoshiki A., Kusakabe M., Ono K., Ida K., Nakayama A., Takahashi M. Tissue-specific carcinogenesis in transgenic mice expressing the RET proto-oncogene with a multiple endocrine neoplasia type 2A mutation. Cancer Res 2000; 60:5254–5260.

    CAS  PubMed  Google Scholar 

  82. Komminoth P., Kunz E.K., Matias-Guiu X., Hiort O., Christiansen G., Colomer, A, Roth J., Heitz P.U. Analysis of RET protooncogene point mutations distinguishes heritable from nonheritable medullary thyroid carcinomas. Cancer 1995; 76:479–489.

    CAS  PubMed  Google Scholar 

  83. Komminoth P., Roth J., Muletta-Feurer S., Saremaslani P., Seelentag W.K., Heitz P.U. RET proto-oncogene point mutations in sporadic neuroendocrine tumors. J Clin Endocrinol Metab 1996; 81:2041–2046.

    Article  CAS  PubMed  Google Scholar 

  84. Kovacs C.S., Mase M., Kovacs K., Nguyen G., Chik C., Thyroid medullary carcinoma with thyroglobulin immunoreactivity in sporadic multiple endocrine neoplasia type 2-B. Cancer 1994; 74:928–932.

    CAS  PubMed  Google Scholar 

  85. Kurokawa K., Iwashita T., Murakami H., Hayashi H., Kawai K., Takahashi M. Identification of SNT/FRS2 docking site on RET receptor tyrosine kinase and its role for signal transduction. Oncogene 2001; 20:1929–1938.

    Article  CAS  PubMed  Google Scholar 

  86. Kurokawa K., Kawai K., Hashimoto M., Ito Y., Takahashi M. Cell signalling and gene expression mediated by RET tyrosine kinase. J Intern Med 2003; 253:627–633.

    Article  CAS  PubMed  Google Scholar 

  87. Lee D.C., Chan K.W., Chan S.Y. RET receptor tyrosine kinase isoforms in kidney function and disease. Oncogene 2002; 21:5582–5592.

    CAS  PubMed  Google Scholar 

  88. Lindor N.M., Honchel R., Kosla S., Thibodeau S.N. Mutations in the RET proto-oncogene in sporadic pheocromocytomas. J Clin Endocrin Metab 1994; 80:627–629.

    Google Scholar 

  89. Lips C.J. Clinical management of the multiple endocrine neoplasia syndromes: results of a computerized opinion poll at the Sixth International Workshop on Multiple Endocrine Neoplasia and von Hippel-Lindau disease. J Intern Med 1998; 243:589–594.

    Article  CAS  PubMed  Google Scholar 

  90. Liu X., Vega Q.C., Decker R.A., Pandey A., Worby C.A., Dixon J.E. Oncogenic RET receptors display different autophosphorylation sites and substrate binding specificities. J Biol Chem 1996; 271:5309–5312.

    CAS  PubMed  Google Scholar 

  91. Lorenzo M.J., Gish G.D., Houghton C., Stonehouse T.J., Pawson T., Ponder B.A.J., Smith D.P. RET alternate splicing influences the interaction of activated RET with the SH2 and PTB domains of Shc, and the SH2 domain of Grb2. Oncogene 1997; 14:763–771.

    Article  CAS  PubMed  Google Scholar 

  92. Manie S., Santoro M., Fusco A., Billaud M. The RET receptor: function in development and dysfunction in congenital malformation. Trends Genet 2001; 17:580–589.

    Article  CAS  PubMed  Google Scholar 

  93. Marcos C., Pachnis V. The effect of the ret-mutation on the normal development of the central and parasympathetic nervous systems. Int J Dev Biol 1996; Suppl 1:137S–138S.:137S–138S.

    Google Scholar 

  94. Marengere L.E., Songyang Z., Gish G.D., Schaller M.D., Parsons J.T., Stern M.J., Cantley L.C., Pawson T. SH2 domain specificity and activity modified by a single residue. Nature 1994; 369:502–505.

    Article  CAS  PubMed  Google Scholar 

  95. Marsh D.J., Robinson B.G., Andrew S., Richardson A.L., Pojer R., Schnitzler M., Mulligan L.M., Hyland V.J. A rapid screening method for the detection of mutations in the RET proto-oncogene in multiple endocrine neoplasia type 2A and familial medullary thyroid carcinoma families. Genomics 1994; 23:477–479.

    Article  CAS  PubMed  Google Scholar 

  96. Melillo R.M., Carlomagno F., De Vita G., Formisano P., Vecchio G., Fusco A., Billaud M., Santoro M. The insulin receptor substrate (IRS)-1 recruits phosphatidylinositol 3-kinase to Ret: evidence for a competition between Shc and IRS-1 for the binding to Ret. Oncogene 2001; 20:209–218.

    Article  CAS  PubMed  Google Scholar 

  97. Mendelsohn J., Baselga J. The EGF receptor family as targets for cancer therapy. Oncogene 2000; 19:6550–6565.

    Article  CAS  PubMed  Google Scholar 

  98. Meng X., Lindahl M., Hyvonen M.E., Parvinen M., de Rooij D.G., Hess M.W., Raatikainen-Ahokas A., Sainio K., Rauvala H., Lakso M., Pichel J.G., Westphal H., Saarma M., Sariola H. Regulation of cell fate decision of undifferentiated spermatogonia by GDNF. Science 2000; 287:1489–1493.

    Article  CAS  PubMed  Google Scholar 

  99. Michiels F.M., Chappuis S., Caillou B., Pasini A., Talbot M., Monier R., Lenoir G.M., Feunteun J., Billaud M. Development of medullary thyroid carcinoma in transgenic mice expressing the RET protooncogene altered by a multiple endocrine neoplasia type 2A mutation. Proc Natl Acad Sci U S A 1997; 94:3330–3335.

    Article  CAS  PubMed  Google Scholar 

  100. Miyauchi A., Futami H., Hai N., Yokozawa T., Kuma K., Aoki N., Kosugi S., Sugano K., Yamaguchi K., Two germline missense mutations at codons 804 and 806 of the RET proto-oncogene in the same allele in a patient with multiple endocrine neoplasia type 2B without codon 918 mutation. Jpn J Cancer Res 1999; 90:1–5.

    CAS  PubMed  Google Scholar 

  101. Mograbi B., Bocciardi R., Bourget I., Juhel T., Farahi-Far D., Romeo G., Ceccherini I., Rossi B. The sensitivity of activated cys ret mutants to glial cell line-derived neurotrophic factor is mandatory to rescue neuroectodermic cells from apoptosis. Mol Cell Biol 2001; 21:6719–6730.

    Article  CAS  PubMed  Google Scholar 

  102. Morita H., Daidoh H., Nagata K., Okano Y., Sudoh Y., Maruyama T., Sarui H., Ishizuka T., Akagi K., Nishisho I., Yasuda K. A family of multiple endocrine neoplasia type 2A: genetic analysis and clinical features. Endocrine J 1996; 43:25–30.

    CAS  Google Scholar 

  103. Mulligan L.M., Gardner E., Smith B.A., Mathew C.G., Ponder B.A. Genetic events in tumour initiation and progression in multiple endocrine neoplasia type 2. Genes Chrom Cancer 1993a; 6:166–177.

    CAS  PubMed  Google Scholar 

  104. Mulligan L.M., Kwok J.B.J., Healey C.S., Elsdon M.J., Eng C., Gardner E., Love D.R., Mole S.E., Moore J.K., Papl L., Ponder M.A., Telenlus H., Tunnacliffe A., Ponder B.A.J. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature 1993b; 363:458–460.

    Article  CAS  PubMed  Google Scholar 

  105. Mulligan L.M., Eng C., Attie T., Lyonnet S., Marsh D.J., Hyland V.J., Robinson B.G., Frilling A., Verellen-Dumoulin C., Safar A. Diverse phenotypes associated with exon 10 mutations of the RET proto-oncogene. Hum Mol Genet 1994; 3:2163–2167.

    CAS  PubMed  Google Scholar 

  106. Mulligan L.M., Ponder B.A. Genetic basis of endocrine disease: multiple endocrine neoplasia type 2. J Clin Endocrinol Metab 1995a; 80:1989–1995.

    CAS  PubMed  Google Scholar 

  107. Mulligan L.M., Marsh D.J., Robinson B.G., Schuffenecker I., Zedenius J., Lips C.J., Gagel R.F., Takai S.I., Noll W.W., Fink M., Genotype-phenotype correlation in multiple endocrine neoplasia type 2: report of the International RET Mutation Consortium. J Intern Med 1995b; 238:343–346.

    CAS  PubMed  Google Scholar 

  108. Murakami H., Yamamura Y., Shimono Y., Kawai K., Kurokawa K., Takahashi M. Role of Dok1 in cell signaling mediated by RET tyrosine kinase. J Biol Chem 2002; 277:32781–32790.

    CAS  PubMed  Google Scholar 

  109. Niccoli-Sire P., Murat A., Rohmer V., Franc S., Chabrier G., Baldet L., Maes B., Savagner F., Giraud S., Bezieau S., Kottler M.L., Morange S., Conte-Devolx B., The French Calcitonin Tumors Group (GETC). Familial medullary thyroid carcinoma with noncysteine ret mutations: phenotype-genotype relationship in a large series of patients. J Clin Endocrinol Metab 2001; 86:3746–3753.

    Article  CAS  PubMed  Google Scholar 

  110. Nicklin S.A., Baker A.H. Tropism-modified adenoviral and adeno-associated viral vectors for gene therapy. Curr Gene Ther 2002; 2:273–293.

    CAS  PubMed  Google Scholar 

  111. Nishikawa M., Murakumo Y., Imai T., Kawai K., Nagaya M., Funahashi H., Nakao A., Takahashi M. Cys61 1Ser mutation in RET proto-oncogene in a kindred with medullary thyroid carcinoma and Hirschsprung’s disease. Eur J Hum Genet 2003; 11:364–368.

    Article  CAS  PubMed  Google Scholar 

  112. Nunziata V., Giannattasio R., Di Giovanni G., D’Armiento M.R., Mancini M. Hereditary localized pruritus in affected members of a kindred with multiple endocrine neoplasia type 2A (Sipple’s syndrome). Clin Endocrinol (Oxf) 1989; 30:57–63.

    CAS  Google Scholar 

  113. Oishi S., Sato T., Takiguchi-Shirahama S., Nakamura Y. Mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Endocrine J 1995; 42:527–536.

    CAS  Google Scholar 

  114. Pachnis V., Mankoo B., Costantini F. Expression of the c-ret proto-oncogene during mouse embryo-genesis. Development 1993; 119:1005–1017.

    CAS  PubMed  Google Scholar 

  115. Pacini F., Fontanelli M., Fugazzola L., Elisei R., Romei C., Di Coscio G., Miccoli P., Pinchera A. Routine measurement of serum calcitonin in nodular thyroid diseases allows the preoperative diagnosis of unsuspected sporadic medullary thyroid carcinoma. J Clin Endocrinol Metab 1994; 78:826–829.

    Article  CAS  PubMed  Google Scholar 

  116. Pandey A., Duan H., Di Fiore P.P., Dixit V.M. The Ret receptor protein tyrosine kinase associates with the SH2-containing adapter protein Grb10. J Biol Chem 1995; 270:21461–21463.

    CAS  PubMed  Google Scholar 

  117. Pandey A., Liu X., Dixon J.E., Di Fiore P.P., Dixit V.M. Direct association between the Ret receptor tyrosine kinase and the Src homology 2-containing adapter protein Grb7. J Biol Chem 1996; 271:10607–10610.

    CAS  PubMed  Google Scholar 

  118. Papotti M., Botto M.F., Favero A., Palestini N., Bussolati G. Poorly differentiated thyroid carcinomas with primordial cell component. A group of aggressive lesions sharing insular, trabecular, and solid patterns. Am J Surg Pathol 1993; 17:291–301.

    CAS  PubMed  Google Scholar 

  119. Paratcha G., Ledda F., Baars L., Coulpier M., Besset V., Anders J., Scott R., Ibanez C.F. Released GFRalpha1 potentiates downstream signaling, neuronal survival, and differentation via a novel mechanism of recruitment of c-Ret to lipid rafts. Neuron 2001; 29:171–184.

    Article  CAS  PubMed  Google Scholar 

  120. Paratcha G., Ledda F., Ibanez C.F. The neural cell adhesion molecule NCAM is an alternative signaling receptor for GDNF family ligands. Cell 2003; 113:867–879.

    Article  CAS  PubMed  Google Scholar 

  121. Pasini A., Geneste O., Legrand P., Schlumberger M., Rossel M., Fournier L., Rudkin B., Schuffenecker I., Lenoir G., Billaud M. Oncogenic activation of RET by two distint FMTC mutations affetting the tirosine kinase domain. Oncogene 1997; 15:393–402.

    Article  CAS  PubMed  Google Scholar 

  122. Pasini B., Ceccherini I., Romeo G. RET mutations in human disease. TIG 1996; 12:138–144.

    CAS  PubMed  Google Scholar 

  123. Pigny P., Bauters C., Wemeau J.L., Houcke M.L., Crepin M., Caron P., Giraud S., Calender A., Buisine M.P., Kerckaert J.P., Porchet N. A novel 9-base pair duplication in RET exon 8 in familial medullary thyroid carcinoma. J Clin Endocrinol Metab 1999; 84:1700–1704.

    Article  CAS  PubMed  Google Scholar 

  124. Ponder BAJ. Multiple endocrine neoplasia type 2. In: Scriver C., Beaudet AL, Sly W, Valle D, editors. The metabolic and molecular bases of inherited disease. New York: 2001: 931–942.

    Google Scholar 

  125. Poteryaev D., Titievsky A., Sun Y.F., Thomas-Crusells J., Lindahl M., Billaud M., Arumae U., Saarma M. GDNF triggers a novel Ret-independent Src kinase family-coupled signaling via a GPI-linked GDNF receptor a1. FEBS 1999; 463:63–66.

    Article  CAS  Google Scholar 

  126. Rey J.M., Brouillet J.P., Fonteneau-Allaire J., Boneu A., Bastie D., Maudelonde T., Pujol P. Novel germline RET mutation segregating with papillary thyroid carcinomas. Genes Chrom Cancer 2001; 32:390–391.

    CAS  PubMed  Google Scholar 

  127. Reynolds L., Jones K., Winton D.J., Cranston A., Houghton C., Howard L., Ponder B.A.J., Smith D.P. C-cell and thyroid apithelial tumours and altered follicular development in transgenic mice expressing the long isoform of MEN 2A RET. Oncogene 2001; 20:3986–3994.

    Article  CAS  PubMed  Google Scholar 

  128. Robledo M., Gil L., Pollan M., Cebrian A., Ruiz S., Azanedo M., Benitez J., Menarguez J., Rojas J.M. Polymorphisms G691S/S904S of RET as genetic modifiers of MEN 2A. Cancer Res 2003; 63:1814–1817.

    CAS  PubMed  Google Scholar 

  129. Romeo G., Ronchetto P., Luo Y., Barone V., Seri M., Ceccherini I., Pasini B., Bocciardi R., Lerone M., Kaariainen H., Martucciello G. Point mutations affecting the tyrosine kinase domain of the RET proto-oncogene in Hirschsprung’s disease. Nature 1994; 367:377–378.

    Article  CAS  PubMed  Google Scholar 

  130. Saarma M. GDNF-a stranger in the TGF-beta superfamily? Eur J Biochem 2000; 267:6968–6971.

    Article  CAS  PubMed  Google Scholar 

  131. Salvatore D., Melillo R.M., Monaco C., Visconti R., Fenzi G., Vecchio G., Fusco A., Santoro M. Increased in vivo phosphorylation of ret tyrosine 1062 is a potential pathogenetic mechanism of multiple endocrine neoplasia type 2B. Cancer Res 2001; 61:1426–1431.

    CAS  PubMed  Google Scholar 

  132. Sanchez M.P., Silos-Santiago I, Frisen J., He B., Lira S.A., Barbacid M. Renal agenesis and the absence of enteric neurons in mice lacking GDNF. Nature 1996; 382:70–73.

    CAS  PubMed  Google Scholar 

  133. Santoro M., Carlomagno F., Hay I.D., Herrmann M.A., Grieco M., Melillo R., Pierotti M.A., Bongarzone I., Delfa Porta G., Berger N., Peix J.L., Paulin C., Fabien N., Vecchio G., Jenkins R.B., Fusco A. Ret oncogene activation in human thyroid neoplasms is restricted to the papillary cancer subtype. J Clin Invest 1992; 89:1517–1522.

    CAS  PubMed  Google Scholar 

  134. Santoro M., Carlomagno F., Romano A., Bottaro D.P., Dathan N.A., Grieco M., Fusco A., Vecchio G., Matoskova B., Kraus M.H., Di Fiore P.P. Activation of RET as a dominant transforming gene by germline mutations of MEN2A and MEN2B. Science 1995; 267:381–383.

    CAS  PubMed  Google Scholar 

  135. Sariola H. The neurotrophic factors in non-neuronal tissues. Cell Mol Life Sci 2001; 58:1061–1066.

    CAS  PubMed  Google Scholar 

  136. Sariola H., Saarma M. GDNF and its receptors in the regulation of the ureteric branching. Int J Develop Biol 1999; 43:413–418.

    CAS  Google Scholar 

  137. Schneider R. The human protooncogene ret: a communicative cadherin? Trends Biochem Sci 1992; 17:468–469.

    Article  CAS  PubMed  Google Scholar 

  138. Schuchardt A., D’Agati V., Larsson-Blomberg L., Costantini F., Pachnis V. Defects in the kidney and enteric nervous system of mice lacking the tyrosine kinase receptor Ret. Nature 1994; 367:380–383.

    Article  CAS  PubMed  Google Scholar 

  139. Segouffin-Cariou C., Billaud M. Transforming ability of MEN2A-RET requires activation of the phosphatidylinositol 3-kinase/AKT signaling pathway. J Biol Chem 2000; 275:3568–3576.

    Article  CAS  PubMed  Google Scholar 

  140. Simons K., Ikonen E. Functional rafts in cell membranes. Nature 1997; 387:569–572.

    Article  CAS  PubMed  Google Scholar 

  141. Sipple J.H. The association of pheochromocytoma with carcinoma of the thyroid gland. Am J Med 1961; 31:163–166.

    Article  Google Scholar 

  142. Smith D.P, Houghton C., Ponder B.A. Germline mutation of RET codon 883 in two cases of de novo MEN 2B. Oncogene 1997; 15:1213–1217.

    Article  CAS  PubMed  Google Scholar 

  143. Smith-Hicks C.L., Sizer K.C., Powers J.F., Tischler A.S., Costantini F. C-cell hyperplasia, pheochro-mocytoma and sympathoadrenal malformation in a mouse model of multiple endocrine neoplasia type 2B. EMBO J 2000; 19:612–622.

    Article  CAS  PubMed  Google Scholar 

  144. Steiner A.L., Goodman A.D., Powers S.R. Study of a kindred with pheochromocytoma, medullary thyroid carcinoma, hyperparathyroidism and Cushing’s disease: multiple endocrine neoplasia, type 2. Medicine (Baltimore) 1968; 47:371–409.

    CAS  Google Scholar 

  145. Tahira T., Ishizaka Y., Itoh F., Sugimura T., Nagao M. Characterization of ret proto-oncogene mRNAs encoding two isoforms of the protein product in a human neuroblastoma cell line. Oncogene 1990; 5:97–102.

    CAS  PubMed  Google Scholar 

  146. Takahashi M., Buma Y., Hiai H. Isolation of Ret proto-oncogene cDNA with an amino-termmal signal sequence. Oncogene 1989; 4:805–806.

    CAS  PubMed  Google Scholar 

  147. Takahashi M., Buma Y., Iwamoto T., Inaguma Y., Ikeda H., Hiai H. Cloning and expression of the ret proto-oncogene encoding a tyrosine kinase with two potential transmembrane domains. Oncogene 1988; 3:571–578.

    CAS  PubMed  Google Scholar 

  148. Takahashi M., Cooper G.M. Ret transforming gene encodes a fusion protein homologous to tyrosine kinases. Mol Cell Biol 1987; 7:1378–1385.

    CAS  PubMed  Google Scholar 

  149. Takahashi M., Iwashita T., Santoro M., Lyonnet S., Lenoir G.M., Billaud M. Co-segregation of MEN2 and Hirschsprung’s disease: the same mutation of RET with both gain and loss-of-function?. Hum Mutat 1999; 13:331–336.

    Article  CAS  PubMed  Google Scholar 

  150. Takahashi M., Ritz J., Cooper G.M. Activation of a novel human transforming gene, ret, by DNA rearrangement. Cell 1985; 42:581–588.

    CAS  PubMed  Google Scholar 

  151. Tessitore A., Sinisi A.A., Pasquali D., Cardone M., Vitale D., Bellastella A., Colantuoni V. A novel case of multiple endocrine neoplasia type 2A associated with two de novo mutations of the RET protooncogene. J Clin Endocrinol Metab 1999; 84:3522–3527.

    Article  CAS  PubMed  Google Scholar 

  152. Treanor J.J., Goodman L., de Sauvage F., Stone D.M., Poulsen K.T., Beck C.D., Gray C., Armanini M.P., Pollock R.A., Hefti F., Phillips H.S., Goddard A., Moore M.W., Buj-Bello A., Davies A.M., Asai N., Takahashi M., Vandlen R., Henderson C.E., Rosenthal A. Characterization of a multicomponent receptor for GDNF Nature 1996; 382:80–83.

    Article  CAS  PubMed  Google Scholar 

  153. Trupp M., Arenas E., Fainzilber M., Nilsson A.S., Sieber A., Grigoriou M., KilKenny C., Salazar-Grueso E., Pachnis V., Arumae U. Functional receptor for GDNF encoded by the c-ret proto-oncogene. Nature 1996; 381:785–788.

    Article  CAS  PubMed  Google Scholar 

  154. Trupp M., Belluardo N., Funakoshi H., Ibanez C.F. Complementary and overlapping expression of glial cell line-derived neurotrophic factor (GDNF), c-ret proto-oncogene, and GDNF receptor-a indicates multiple mechanisms of trophic actions in the adult Rat CNS. J Neurosci 1997; 17:3554–3567.

    CAS  PubMed  Google Scholar 

  155. Trupp M., Scott R., Whittemore S.R., Ibanez C.F. Ret-dependent and-independent mechanisms of glial cell line-derived neurotrophic factor signaling in neuronal cells. J Biol Chem 1999; 274:20885–20894.

    Article  CAS  PubMed  Google Scholar 

  156. Tsui-Pierchala B.A., Ahrens R.C., Crowder R.J., Milbrandt J., Johnson E.M. Jr. The long and short isoforms of Ret function as independent signaling complexes. J Biol Chem 2002; 277:34618–34625.

    Article  CAS  PubMed  Google Scholar 

  157. Tsuzuki T., Takahashi M., Asai N., Iwashita T., Matsuyama M., Asai J. Spatial and temporal expression of the RET proto-oncogene product in embryonic, infant and adult rat tissues. Oncogene 1995; 10:191–198.

    CAS  PubMed  Google Scholar 

  158. Vega Q.C., Worby C.A., Lechner M.S., Dixon J.E., Dressler G.R. Glial cell line-derived neurotrophic factor activates the receptor tyrosine kinase RET and promotes kidney morphogenesis. Proc Natl Acad Sci USA 1996; 93:10657–10661.

    Article  CAS  PubMed  Google Scholar 

  159. Verdy M., Weber A.M., Roy C.C., Morin C.L., Cadotte M., Brochu P. Hirschsprung’s disease in a family with multiple endocrine neoplasia type 2. J Pediatr Gastroenterol Nutr 1982; 1:603–607.

    CAS  PubMed  Google Scholar 

  160. Watanabe T., Ichihara M., Hashimoto M., Shimono K., Shimoyama Y., Nagasaka T., Murakumo Y., Murakami H., Sugiura H., Iwata H., Ishiguro N., Takahashi M. Characterization of gene expression induced by RET with MEN2A or MEN2B mutation. Am J Pathol 2002; 161:249–256.

    CAS  PubMed  Google Scholar 

  161. Wickham T.J. Ligand-directed targeting of genes to the site of disease. Nat Med 2003; 9:135–139.

    Article  CAS  PubMed  Google Scholar 

  162. Williams E.D. Histogenesis of medullary carcinoma of the thyroid. J Clin Pathol 1966; 19:114–118.

    CAS  PubMed  Google Scholar 

  163. Williams E.D., Pollock D.J. Multiple mucosal neuromata with endocrine tumours: a syndrome allied to von Recklinghausen’s disease. J Pathol Bacteriol 1966; 91:71–80.

    Article  CAS  PubMed  Google Scholar 

  164. Wohllk N., Cote G.J., Bugalho M.M., Ordonez N., Evans D.B., Goepfert H., Khorana S., Schultz P., Richards C.S., Gagel R.F. Relevance of RET proto-oncogene mutations in sporadic medullary thyroid carcinoma. J Clin Endocrinol Metab 1996; 81:3740–3745.

    Article  CAS  PubMed  Google Scholar 

  165. Worley D.S., Pisano J.M., Choi E.D., Walus L., Hession C.A., Cate R.L., Sanicola M., Birren S.J. Developmental regulation of GDNF response and receptor expression in the enteric nervous system. Development 2000; 127:4383–4393.

    CAS  PubMed  Google Scholar 

  166. Young H.M., Hearn C.J., Ciampoli D., Southwell B.R., Brunet J.F., Newgreen D.F. A single rostrocaudal colonization of the rodent intestine by enteric neuron precursors is revealed by the expression of Phox2b, Ret, and p75 and by explants grown under the kidney capsule or in organ culture. Dev Biol 1998; 202:67–84.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Experimental Oncology Operative Unit #3. Via G. Venezian, Istituto Nazionale Tumori, 1 20133, Milan, Italy

    Marco A. Pierotti, Elena Arighi, Debora Degl’innocenti & Maria Grazia Borrello

Authors
  1. Marco A. Pierotti
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Elena Arighi
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Debora Degl’innocenti
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Maria Grazia Borrello
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Osancor Biotech, Inc., Watford, WD17 3BY, Herts, UK

    Nadir R. Farid

Rights and permissions

Reprints and permissions

Copyright information

© 2005 Springer Science + Business Media, Inc.

About this chapter

Cite this chapter

Pierotti, M.A., Arighi, E., Degl’innocenti, D., Borrello, M.G. (2005). Ret Activation in Medullary Carcinomas. In: Farid, N.R. (eds) Molecular Basis of Thyroid Cancer. Cancer Treatment and Research, vol 122. Springer, Boston, MA. https://doi.org/10.1007/1-4020-8107-3_23

Download citation

  • DOI: https://doi.org/10.1007/1-4020-8107-3_23

  • Publisher Name: Springer, Boston, MA

  • Print ISBN: 978-1-4020-8106-4

  • Online ISBN: 978-1-4020-8107-1

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation