Download PDF
Horm Metab Res 2009; 41(6): 488-499
DOI: 10.1055/s-0029-1215572
Review

© Georg Thieme Verlag KG Stuttgart · New York

Modeling Thyroid Cancer in the Mouse

X-G. Zhu 1 , S-Y. Cheng 1
  • 1Laboratory of Molecular Biology, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD, USA
Further Information

Publication History

received 02.02.2009

accepted 03.03.2009

Publication Date:
08 April 2009 (online)

Also available at
    Permissions and Reprints

Abstract

Thyroid carcinomas, the most common endocrine tumors in humans, have an increasing incidence in the U.S. and worldwide. There are four major types of thyroid cancers: papillary, follicular, anaplastic, and medullary carcinomas. In recent years, significant progress has been made in the identification of genetic alterations in thyroid carcinomas, particularly, papillary and medullary thyroid cancers. Mouse models of thyroid cancer are valuable tools in elucidating molecular genetic changes underlying thyroid carcinogenesis and in identifying potential molecular targets for therapeutic intervention. Representative mouse models of papillary, follicular, and medullary carcinomas are reviewed here with particular emphasis on those for follicular thyroid carcinomas. Challenges for further development in the modeling of thyroid cancer will also be discussed.

Key words

thyroid cancer - thyroid hormone - mouse models

References

  • 1 Nikiforova MN, Nikiforov YE. Molecular genetics of thyroid cancer: implications for diagnosis, treatment and prognosis.  Expert Rev Mol Diagn. 2008;  8 83-95
    Google Scholar
  • 2 Jemal A, Siegel R, Ward E, Hao Y, Xu J, Murray T, Thun MJ. Cancer statistics, 2008.  CA Cancer J Clin. 2008;  58 71-96
    Google Scholar
  • 3 Lodish MB, Stratakis CA. RET oncogene in MEN2, MEN2B, MTC and other forms of thyroid cancer.  Expert Rev Anticancer Ther. 2008;  8 625-632
    Google Scholar
  • 4 Mauchamp J, Mirrione A, Alquier C, Andre F. Follicle-like structure and polarized monolayer: role of the extracellular matrix on thyroid cell organization in primary culture.  Biol Cell. 1998;  90 369-380
    Google Scholar
  • 5 De Felice M, Di Lauro R. Thyroid development and its disorders: genetics and molecular mechanisms.  Endocr Rev. 2004;  25 722-746
    Google Scholar
  • 6 Lazzaro D, Price M, de Felice M, Di Lauro R. The transcription factor TTF-1 is expressed at the onset of thyroid and lung morphogenesis and in restricted regions of the foetal brain.  Development. 1991;  113 1093-1104
    Google Scholar
  • 7 Postiglione MP, Parlato R, Rodriguez-Mallon A, Rosica A, Mithbaokar P, Maresca M, Marians RC, Davies TF, Zannini MS, De Felice M, Di Lauro R. Role of the thyroid-stimulating hormone receptor signaling in development and differentiation of the thyroid gland.  Proc Natl Acad Sci USA. 2002;  99 15462-15467
    Google Scholar
  • 8 Meunier D, Aubin J, Jeannotte L. Perturbed thyroid morphology and transient hypothyroidism symptoms in Hoxa5 mutant mice.  Dev Dyn. 2003;  227 367-378
    Google Scholar
  • 9 Castellone MD, Santoro M. Dysregulated RET signaling in thyroid cancer.  Endocrinol Metab Clin North Am. 2008;  37 363-374 , viii
    Google Scholar
  • 10 Nikiforov YE. RET/PTC rearrangement in thyroid tumors.  Endocr Pathol. 2002;  13 3-16
    Google Scholar
  • 11 Nikiforova MN, Stringer JR, Blough R, Medvedovic M, Fagin JA, Nikiforov YE. Proximity of chromosomal loci that participate in radiation-induced rearrangements in human cells.  Science. 2000;  290 138-141
    Google Scholar
  • 12 Grieco M, Santoro M, Berlingieri MT, Melillo RM, Donghi R, Bongarzone I, Pierotti MA, 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
    Google Scholar
  • 13 Bongarzone I, Butti MG, Coronelli S, Borrello MG, Santoro M, Mondellini P, Pilotti S, Fusco A, Della Porta G, Pierotti MA. Frequent activation of ret protooncogene by fusion with a new activating gene in papillary thyroid carcinomas.  Cancer Res. 1994;  54 2979-2985
    Google Scholar
  • 14 Boice Jr JD. Radiation-induced thyroid cancer – what’s new?.  J Natl Cancer Inst. 2005;  97 703-705
    Google Scholar
  • 15 Cardis E, Kesminiene A, Ivanov V, Malakhova I, Shibata Y, Khrouch V, Drozdovitch V, Maceika E, Zvonova I, Vlassov O, Bouville A, Goulko G, Hoshi M, Abrosimov A, Anoshko J, Astakhova L, Chekin S, Demidchik E, Galanti R, Ito M, Korobova E, Lushnikov E, Maksioutov M, Masyakin V, Nerovnia A, Parshin V, Parshkov E, Piliptsevich N, Pinchera A, Polyakov S, Shabeka N, Suonio E, Tenet V, Tsyb A, Yamashita S, Williams D. Risk of thyroid cancer after exposure to 131I in childhood.  J Natl Cancer Inst. 2005;  97 724-732
    Google Scholar
  • 16 Klugbauer S, Lengfelder E, Demidchik EP, Rabes HM. High prevalence of RET rearrangement in thyroid tumors of children from Belarus after the Chernobyl reactor accident.  Oncogene. 1995;  11 2459-2467
    Google Scholar
  • 17 Tallini G. Molecular pathobiology of thyroid neoplasms.  Endocr Pathol. 2002;  13 271-288
    Google Scholar
  • 18 Bongarzone I, Fugazzola L, Vigneri P, Mariani L, Mondellini P, Pacini F, Basolo F, Pinchera A, Pilotti S, Pierotti MA. Age-related activation of the tyrosine kinase receptor protooncogenes RET and NTRK1 in papillary thyroid carcinoma.  J Clin Endocrinol Metab. 1996;  81 2006-2009
    Google Scholar
  • 19 Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA. High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC-RAS-BRAF signaling pathway in papillary thyroid carcinoma.  Cancer Res. 2003;  63 1454-1457
    Google Scholar
  • 20 Namba H, Rubin SA, Fagin JA. Point mutations of ras oncogenes are an early event in thyroid tumorigenesis.  Mol Endocrinol. 1990;  4 1474-1479
    Google Scholar
  • 21 Benvenga S. Update on thyroid cancer.  Horm Metab Res. 2008;  40 323-328
    Google Scholar
  • 22 Davies H, Bignell GR, Cox C, Stephens P, Edkins S, Clegg S, Teague J, Woffendin H, Garnett MJ, Bottomley W, Davis N, Dicks E, Ewing R, Floyd Y, Gray K, Hall S, Hawes R, Hughes J, Kosmidou V, Menzies A, Mould C, Parker A, Stevens C, Watt S, Hooper S, Wilson R, Jayatilake H, Gusterson BA, Cooper C, Shipley J, Hargrave D, Pritchard-Jones K, Maitland N, Chenevix-Trench G, Riggins GJ, Bigner DD, Palmieri G, Cossu A, Flanagan A, Nicholson A, Ho JW, Leung SY, Yuen ST, Weber BL, Seigler HF, Darrow TL, Paterson H, Marais R, Marshall CJ, Wooster R, Stratton MR, Futreal PA. Mutations of the BRAF gene in human cancer.  Nature. 2002;  417 949-954
    Google Scholar
  • 23 Ciampi R, Nikiforov YE. RET/PTC rearrangements and BRAF mutations in thyroid tumorigenesis.  Endocrinology. 2007;  148 936-941
    Google Scholar
  • 24 Saxena N, Lahiri SS, Hambarde S, Tripathi RP. RAS: target for cancer therapy.  Cancer Invest. 2008;  26 948-955
    Google Scholar
  • 25 Riesco-Eizaguirre G, Santisteban P. New insights in thyroid follicular cell biology and its impact in thyroid cancer therapy.  Endocr Relat Cancer. 2007;  14 957-977
    Google Scholar
  • 26 Quayle FJ, Moley JF. Medullary thyroid carcinoma: including MEN 2A and MEN 2B syndromes.  J Surg Oncol. 2005;  89 122-129
    Google Scholar
  • 27 Gimm O, Dralle H. C-cell cancer – prevention and treatment.  Langenbecks Arch Surg. 1999;  384 16-23
    Google Scholar
  • 28 Michiels FM, Chappuis S, Caillou B, Pasini A, Talbot M, Monier R, Lenoir GM, 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 USA. 1997;  94 3330-3335
    Google Scholar
  • 29 Esapa CT, Johnson SJ, Kendall-Taylor P, Lennard TW, Harris PE. Prevalence of Ras mutations in thyroid neoplasia.  Clin Endocrinol (Oxf). 1999;  50 529-535
    Google Scholar
  • 30 Motoi N, Sakamoto A, Yamochi T, Horiuchi H, Motoi T, Machinami R. Role of ras mutation in the progression of thyroid carcinoma of follicular epithelial origin.  Pathol Res Pract. 2000;  196 1-7
    Google Scholar
  • 31 Suarez HG, du Villard JA, Severino M, Caillou B, Schlumberger M, Tubiana M, Parmentier C, Monier R. Presence of mutations in all three ras genes in human thyroid tumors.  Oncogene. 1990;  5 565-570
    Google Scholar
  • 32 Basolo F, Pisaturo F, Pollina LE, Fontanini G, Elisei R, Molinaro E, Iacconi P, Miccoli P, Pacini F. N-ras mutation in poorly differentiated thyroid carcinomas: correlation with bone metastases and inverse correlation to thyroglobulin expression.  Thyroid. 2000;  10 19-23
    Google Scholar
  • 33 Saavedra HI, Knauf JA, Shirokawa JM, Wang J, Ouyang B, Elisei R, Stambrook PJ, Fagin JA. The RAS oncogene induces genomic instability in thyroid PCCL3 cells via the MAPK pathway.  Oncogene. 2000;  19 3948-3954
    Google Scholar
  • 34 Dwight T, Thoppe SR, Foukakis T, Lui WO, Wallin G, Hoog A, Frisk T, Larsson C, Zedenius J. Involvement of the PAX8/peroxisome proliferator-activated receptor gamma rearrangement in follicular thyroid tumors.  J Clin Endocrinol Metab. 2003;  88 4440-4445
    Google Scholar
  • 35 French CA, Alexander EK, Cibas ES, Nose V, Laguette J, Faquin W, Garber J, Moore Jr F, Fletcher JA, Larsen PR, Kroll TG. Genetic and biological subgroups of low-stage follicular thyroid cancer.  Am J Pathol. 2003;  162 1053-1060
    Google Scholar
  • 36 Nikiforova MN, Lynch RA, Biddinger PW, Alexander EK, Dorn 2nd GW, Tallini G, Kroll TG, Nikiforov YE. RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma.  J Clin Endocrinol Metab. 2003;  88 2318-2326
    Google Scholar
  • 37 Kroll TG, Sarraf P, Pecciarini L, Chen CJ, Mueller E, Spiegelman BM, Fletcher JA. PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected].  Science. 2000;  289 1357-1360
    Google Scholar
  • 38 Placzkowski KA, Reddi HV, Grebe SK, Eberhardt NL, McIver B. The role of the PAX8/PPARgamma fusion oncogene in thyroid cancer.  PPAR Res. 2008;  , Oct 29 [Epub ahead of print]
    Google Scholar
  • 39 Gandolfi PP, Frisina A, Raffa M, Renda F, Rocchetti O, Ruggeri C, Tombolini A. The incidence of thyroid carcinoma in multinodular goiter: retrospective analysis.  Acta Biomed. 2004;  75 114-117
    Google Scholar
  • 40 Lawal O, Agbakwuru A, Olayinka OS, Adelusola K. Thyroid malignancy in endemic nodular goitres: prevalence, pattern and treatment.  Eur J Surg Oncol. 2001;  27 157-161
    Google Scholar
  • 41 Rivas M, Santisteban P. TSH-activated signaling pathways in thyroid tumorigenesis.  Mol Cell Endocrinol. 2003;  213 31-45
    Google Scholar
  • 42 Ward JM, Ohshima M. The role of iodine in carcinogenesis.  Adv Exp Med Biol. 1986;  206 529-542
    Google Scholar
  • 43 Mack WJ, Preston-Martin S, Bernstein L, Qian D, Xiang M. Reproductive and hormonal risk factors for thyroid cancer in Los Angeles County females.  Cancer Epidemiol Biomarkers Prev. 1999;  8 991-997
    Google Scholar
  • 44 Rios A, Rodriguez JM, Canteras M, Galindo PJ, Balsalobre MD, Parrilla P. Risk factors for malignancy in multinodular goitres.  Eur J Surg Oncol. 2004;  30 58-62
    Google Scholar
  • 45 Truong T, Orsi L, Dubourdieu D, Rougier Y, Hemon D, Guenel P. Role of goiter and of menstrual and reproductive factors in thyroid cancer: a population-based case-control study in New Caledonia (South Pacific), a very high incidence area.  Am J Epidemiol. 2005;  161 1056-1065
    Google Scholar
  • 46 Capen CC. Overview of structural and functional lesions in endocrine organs of animals.  Toxicol Pathol. 2001;  29 8-33
    Google Scholar
  • 47 Capen CC. Mechanistic data and risk assessment of selected toxic end points of the thyroid gland.  Toxicol Pathol. 1997;  25 39-48
    Google Scholar
  • 48 Ledent C, Denef JF, Cottecchia S, Lefkowitz R, Dumont J, Vassart G, Parmentier M. Costimulation of adenylyl cyclase and phospholipase C by a mutant alpha 1B-adrenergic receptor transgene promotes malignant transformation of thyroid follicular cells.  Endocrinology. 1997;  138 369-378
    Google Scholar
  • 49 Ledent C, Marcotte A, Dumont JE, Vassart G, Parmentier M. Differentiated carcinomas develop as a consequence of the thyroid specific expression of a thyroglobulin-human papillomavirus type 16 E7 transgene.  Oncogene. 1995;  10 1789-1797
    Google Scholar
  • 50 Ledent C, Dumont JE, Vassart G, Parmentier M. Thyroid expression of an A2 adenosine receptor transgene induces thyroid hyperplasia and hyperthyroidism.  EMBO J. 1992;  11 537-542
    Google Scholar
  • 51 Mazzaferri EL. Management of a solitary thyroid nodule.  N Engl J Med. 1993;  328 553-559
    Google Scholar
  • 52 Michiels FM, Caillou B, Talbot M, Dessarps-Freichey F, Maunoury MT, Schlumberger M, Mercken L, Monier R, Feunteun J. Oncogenic potential of guanine nucleotide stimulatory factor alpha subunit in thyroid glands of transgenic mice.  Proc Natl Acad Sci USA. 1994;  91 10488-10492
    Google Scholar
  • 53 Zeiger MA, Saji M, Gusev Y, Westra WH, Takiyama Y, Dooley WC, Kohn LD, Levine MA. Thyroid-specific expression of cholera toxin A1 subunit causes thyroid hyperplasia and hyperthyroidism in transgenic mice.  Endocrinology. 1997;  138 3133-3140
    Google Scholar
  • 54 Chevillard S, Ugolin N, Vielh P, Ory K, Levalois C, Elliott D, Clayman GL, El-Naggar AK. Gene expression profiling of differentiated thyroid neoplasms: diagnostic and clinical implications.  Clin Cancer Res. 2004;  10 6586-6597
    Google Scholar
  • 55 Ying H, Suzuki H, Furumoto H, Walker R, Meltzer P, Willingham MC, Cheng SY. Alterations in genomic profiles during tumor progression in a mouse model of follicular thyroid carcinoma.  Carcinogenesis. 2003;  24 1467-1479
    Google Scholar
  • 56 Kato Y, Ying H, Zhao L, Furuya F, Araki O, Willingham MC, Cheng SY. PPARgamma insufficiency promotes follicular thyroid carcinogenesis via activation of the nuclear factor-kappaB signaling pathway.  Oncogene. 2006;  25 2736-2747
    Google Scholar
  • 57 Hosal SA, Apel RL, Freeman JL, Azadian A, Rosen IB, LiVolsi VA, Asa SL. Immunohistochemical Localization of p53 in Human Thyroid Neoplasms: Correlation with Biological Behavior.  Endocr Pathol. 1997;  8 21-28
    Google Scholar
  • 58 Nikiforov YE. Genetic alterations involved in the transition from well-differentiated to poorly differentiated and anaplastic thyroid carcinomas.  Endocr Pathol. 2004;  15 319-327
    Google Scholar
  • 59 Quiros RM, Ding HG, Gattuso P, Prinz RA, Xu X. Evidence that one subset of anaplastic thyroid carcinomas are derived from papillary carcinomas due to BRAF and p53 mutations.  Cancer. 2005;  103 2261-2268
    Google Scholar
  • 60 Garcia-Rostan G, Tallini G, Herrero A, D’Aquila TG, Carcangiu ML, Rimm DL. Frequent mutation and nuclear localization of beta-catenin in anaplastic thyroid carcinoma.  Cancer Res. 1999;  59 1811-1815
    Google Scholar
  • 61 Jhiang SM, Sagartz JE, Tong Q, Parker-Thornburg J, Capen CC, Cho JY, Xing S, Ledent C. Targeted expression of the ret/PTC1 oncogene induces papillary thyroid carcinomas.  Endocrinology. 1996;  137 375-378
    Google Scholar
  • 62 Cho JY, Sagartz JE, Capen CC, Mazzaferri EL, Jhiang SM. Early cellular abnormalities induced by RET/PTC1 oncogene in thyroid-targeted transgenic mice.  Oncogene. 1999;  18 3659-3665
    Google Scholar
  • 63 Santoro M, Chiappetta G, Cerrato A, Salvatore D, Zhang L, Manzo G, Picone A, Portella G, Santelli G, Vecchio G, Fusco A. Development of thyroid papillary carcinomas secondary to tissue-specific expression of the RET/PTC1 oncogene in transgenic mice.  Oncogene. 1996;  12 1821-1826
    Google Scholar
  • 64 Sagartz JE, Jhiang SM, Tong Q, Capen CC. Thyroid-stimulating hormone promotes growth of thyroid carcinomas in transgenic mice with targeted expression of the ret/PTC1 oncogene.  Lab Invest. 1997;  76 307-318
    Google Scholar
  • 65 La Perle KM, Jhiang SM, Capen CC. Loss of p53 promotes anaplasia and local invasion in ret/PTC1-induced thyroid carcinomas.  Am J Pathol. 2000;  157 671-677
    Google Scholar
  • 66 Powell Jr DJ, Russell J, Nibu K, Li G, Rhee E, Liao M, Goldstein M, Keane WM, Santoro M, Fusco A, Rothstein JL. The RET/PTC3 oncogene: metastatic solid-type papillary carcinomas in murine thyroids.  Cancer Res. 1998;  58 5523-5528
    Google Scholar
  • 67 Burniat A, Jin L, Detours V, Driessens N, Goffard JC, Santoro M, Rothstein J, Dumont JE, Miot F, Corvilain B. Gene expression in RET/PTC3 and E7 transgenic mouse thyroids: RET/PTC3 but not E7 tumors are partial and transient models of human papillary thyroid cancers.  Endocrinology. 2008;  149 5107-5117
    Google Scholar
  • 68 Jin L, Burniat A, Dumont JE, Miot F, Corvilain B, Franc B. Human thyroid tumours, the puzzling lessons from E7 and RET/PTC3 transgenic mice.  Br J Cancer. 2008;  99 1874-1883
    Google Scholar
  • 69 Knauf JA, Ma X, Smith EP, Zhang L, Mitsutake N, Liao XH, Refetoff S, Nikiforov YE, Fagin JA. Targeted expression of BRAFV600E in thyroid cells of transgenic mice results in papillary thyroid cancers that undergo dedifferentiation.  Cancer Res. 2005;  65 4238-4245
    Google Scholar
  • 70 Xing M. BRAF mutation in thyroid cancer.  Endocr Relat Cancer. 2005;  12 245-262
    Google Scholar
  • 71 Russell JP, Powell DJ, Cunnane M, Greco A, Portella G, Santoro M, Fusco A, Rothstein JL. The TRK-T1 fusion protein induces neoplastic transformation of thyroid epithelium.  Oncogene. 2000;  19 5729-5735
    Google Scholar
  • 72 Feunteun J, Michiels F, Rochefort P, Caillou B, Talbot M, Fournes B, Mercken L, Schlumberger M, Monier R. Targeted oncogenesis in the thyroid of transgenic mice.  Horm Res. 1997;  47 137-139
    Google Scholar
  • 73 Rochefort P, Caillou B, Michiels FM, Ledent C, Talbot M, Schlumberger M, Lavelle F, Monier R, Feunteun J. Thyroid pathologies in transgenic mice expressing a human activated Ras gene driven by a thyroglobulin promoter.  Oncogene. 1996;  12 111-118
    Google Scholar
  • 74 Vitagliano D, Portella G, Troncone G, Francione A, Rossi C, Bruno A, Giorgini A, Coluzzi S, Nappi TC, Rothstein JL, Pasquinelli R, Chiappetta G, Terracciano D, Macchia V, Melillo RM, Fusco A, Santoro M. Thyroid targeting of the N-ras(Gln61Lys) oncogene in transgenic mice results in follicular tumors that progress to poorly differentiated carcinomas.  Oncogene. 2006;  25 5467-5474
    Google Scholar
  • 75 Coppee F, Gerard AC, Denef JF, Ledent C, Vassart G, Dumont JE, Parmentier M. Early occurrence of metastatic differentiated thyroid carcinomas in transgenic mice expressing the A2a adenosine receptor gene and the human papillomavirus type 16 E7 oncogene.  Oncogene. 1996;  13 1471-1482
    Google Scholar
  • 76 Santelli G, de Franciscis V, Portella G, Chiappetta G, D’Alessio A, Califano D, Rosati R, Mineo A, Monaco C, Manzo G, Pozzi L, Vecchio G. Production of transgenic mice expressing the Ki-ras oncogene under the control of a thyroglobulin promoter.  Cancer Res. 1993;  53 5523-5527
    Google Scholar
  • 77 Ribeiro-Neto F, Leon A, Urbani-Brocard J, Lou L, Nyska A, Altschuler DL. cAMP-dependent oncogenic action of Rap1b in the thyroid gland.  J Biol Chem. 2004;  279 46868-46875
    Google Scholar
  • 78 Yen PM. Molecular basis of resistance to thyroid hormone.  Trends Endocrinol Metab. 2003;  14 327-333
    Google Scholar
  • 79 Ono S, Schwartz ID, Mueller OT, Root AW, Usala SJ, Bercu BB. Homozygosity for a dominant negative thyroid hormone receptor gene responsible for generalized resistance to thyroid hormone.  J Clin Endocrinol Metab. 1991;  73 990-994
    Google Scholar
  • 80 Kaneshige M, Kaneshige K, Zhu X, Dace A, Garrett L, Carter TA, Kazlauskaite R, Pankratz DG, Wynshaw-Boris A, Refetoff S, Weintraub B, Willingham MC, Barlow C, Cheng S. Mice with a targeted mutation in the thyroid hormone beta receptor gene exhibit impaired growth and resistance to thyroid hormone.  Proc Natl Acad Sci USA. 2000;  97 13209-13214
    Google Scholar
  • 81 Parrilla R, Mixson AJ, McPherson JA, MacClaskey JH, Weintraub BD. Characterization of seven novel mutations of the c-erbA beta gene in unrelated kindreds with generalized thyroid hormone resistance. Evidence for two “hot spot” regions of the ligand binding domain.  J Clin Invest. 1991;  88 2123-2130
    Google Scholar
  • 82 Suzuki H, Willingham MC, Cheng SY. Mice with a mutation in the thyroid hormone receptor beta gene spontaneously develop thyroid carcinoma: a mouse model of thyroid carcinogenesis.  Thyroid. 2002;  12 963-969
    Google Scholar
  • 83 Ying H, Suzuki H, Zhao L, Willingham MC, Meltzer P, Cheng SY. Mutant thyroid hormone receptor beta represses the expression and transcriptional activity of peroxisome proliferator-activated receptor gamma during thyroid carcinogenesis.  Cancer Res. 2003;  63 5274-5280
    Google Scholar
  • 84 Kim CS, Vasko VV, Kato Y, Kruhlak M, Saji M, Cheng SY, Ringel MD. AKT activation promotes metastasis in a mouse model of follicular thyroid carcinoma.  Endocrinology. 2005;  146 4456-4463
    Google Scholar
  • 85 Furuya F, Guigon CJ, Zhao L, Lu C, Hanover JA, Cheng SY. Nuclear receptor corepressor is a novel regulator of phosphatidylinositol 3-kinase signaling.  Mol Cell Biol. 2007;  27 6116-6126
    Google Scholar
  • 86 Furuya F, Hanover JA, Cheng SY. Activation of phosphatidylinositol 3-kinase signaling by a mutant thyroid hormone beta receptor.  Proc Natl Acad Sci USA. 2006;  103 1780-1785
    Google Scholar
  • 87 Furuya F, Lu C, Willingham MC, Cheng SY. Inhibition of phosphatidylinositol 3-kinase delays tumor progression and blocks metastatic spread in a mouse model of thyroid cancer.  Carcinogenesis. 2007;  28 2451-2458
    Google Scholar
  • 88 Ying H, Furuya F, Zhao L, Araki O, West BL, Hanover JA, Willingham MC, Cheng SY. Aberrant accumulation of PTTG1 induced by a mutated thyroid hormone beta receptor inhibits mitotic progression.  J Clin Invest. 2006;  116 2972-2984
    Google Scholar
  • 89 Zimonjic DB, Kato Y, Ying H, Popescu NC, Cheng SY. Chromosomal aberrations in cell lines derived from thyroid tumors spontaneously developed in TRbetaPV/PV mice.  Cancer Genet Cytogenet. 2005;  161 104-109
    Google Scholar
  • 90 Kim CS, Ying H, Willingham MC, Cheng SY. The pituitary tumor-transforming gene promotes angiogenesis in a mouse model of follicular thyroid cancer.  Carcinogenesis. 2007;  28 932-939
    Google Scholar
  • 91 Kim CS, Furuya F, Ying H, Kato Y, Hanover JA, Cheng SY. Gelsolin: a novel thyroid hormone receptor-beta interacting protein that modulates tumor progression in a mouse model of follicular thyroid cancer.  Endocrinology. 2007;  148 1306-1312
    Google Scholar
  • 92 Torres-Arzayus MI, Font de Mora J, Yuan J, Vazquez F, Bronson R, Rue M, Sellers WR, Brown M. High tumor incidence and activation of the PI3K/AKT pathway in transgenic mice define AIB1 as an oncogene.  Cancer Cell. 2004;  6 263-274
    Google Scholar
  • 93 Ying H, Willingham MC, Cheng SY. The steroid receptor coactivator-3 is a tumor promoter in a mouse model of thyroid cancer.  Oncogene. 2008;  27 823-830
    Google Scholar
  • 94 Furuya F, Ying H, Zhao L, Cheng SY. Novel functions of thyroid hormone receptor mutants: beyond nucleus-initiated transcription.  Steroids. 2007;  72 171-179
    Google Scholar
  • 95 Guigon CJ, Zhao L, Lu C, Willingham MC, Cheng SY. Regulation of beta-catenin by a novel nongenomic action of thyroid hormone beta receptor.  Mol Cell Biol. 2008;  28 4598-4608
    Google Scholar
  • 96 Kato Y, Ying H, Willingham MC, Cheng SY. A tumor suppressor role for thyroid hormone beta receptor in a mouse model of thyroid carcinogenesis.  Endocrinology. 2004;  145 4430-4438
    Google Scholar
  • 97 Ledent C, Dumont J, Vassart G, Parmentier M. Thyroid adenocarcinomas secondary to tissue-specific expression of simian virus-40 large T-antigen in transgenic mice.  Endocrinology. 1991;  129 1391-1401
    Google Scholar
  • 98 Mulligan LM, Kwok JB, Healey CS, Elsdon MJ, Eng C, Gardner E, Love DR, Mole SE, Moore JK, Papi L, Ponder MA, Telenius H, Tunnacliffe A, Ponder BAJ. Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A.  Nature. 1993;  363 458-460
    Google Scholar
  • 99 Harvey M, Vogel H, Lee EY, Bradley A, Donehower LA. Mice deficient in both p53 and Rb develop tumors primarily of endocrine origin.  Cancer Res. 1995;  55 1146-1151
    Google Scholar
  • 100 Ziebold U, Lee EY, Bronson RT, Lees JA. E2F3 loss has opposing effects on different pRB-deficient tumors, resulting in suppression of pituitary tumors but metastasis of medullary thyroid carcinomas.  Mol Cell Biol. 2003;  23 6542-6552
    Google Scholar
  • 101 Coxon AB, Ward JM, Geradts J, Otterson GA, Zajac-Kaye M, Kaye FJ. RET cooperates with RB/p53 inactivation in a somatic multi-step model for murine thyroid cancer.  Oncogene. 1998;  17 1625-1628
    Google Scholar
  • 102 Nakagawa T, Mabry M, de Bustros A, Ihle JN, Nelkin BD, Baylin SB. Introduction of v-Ha-ras oncogene induces differentiation of cultured human medullary thyroid carcinoma cells.  Proc Natl Acad Sci USA. 1987;  84 5923-5927
    Google Scholar
  • 103 Johnston D, Hatzis D, Sunday ME. Expression of v-Ha-ras driven by the calcitonin/calcitonin gene-related peptide promoter: a novel transgenic murine model for medullary thyroid carcinoma.  Oncogene. 1998;  16 167-177
    Google Scholar
  • 104 Cranston AN, Ponder BA. Modulation of medullary thyroid carcinoma penetrance suggests the presence of modifier genes in a RET transgenic mouse model.  Cancer Res. 2003;  63 4777-4780
    Google Scholar
  • 105 Jackson EL, Willis N, Mercer K, Bronson RT, Crowley D, Montoya R, Jacks T, Tuveson DA. Analysis of lung tumor initiation and progression using conditional expression of oncogenic K-ras.  Genes Dev. 2001;  15 3243-3248
    Google Scholar
  • 106 Lakso M, Sauer B, Mosinger Jr B, Lee EJ, Manning RW, Yu SH, Mulder KL, Westphal H. Targeted oncogene activation by site-specific recombination in transgenic mice.  Proc Natl Acad Sci USA. 1992;  89 6232-6236
    Google Scholar
  • 107 Johnson L, Mercer K, Greenbaum D, Bronson RT, Crowley D, Tuveson DA, Jacks T. Somatic activation of the K-ras oncogene causes early onset lung cancer in mice.  Nature. 2001;  410 1111-1116
    Google Scholar
  • 108 Smith AJ, De Sousa MA, Kwabi-Addo B, Heppell-Parton A, Impey H, Rabbitts P. A site-directed chromosomal translocation induced in embryonic stem cells by Cre-loxP recombination.  Nat Genet. 1995;  9 376-385
    Google Scholar
  • 109 Buchholz F, Refaeli Y, Trumpp A, Bishop JM. Inducible chromosomal translocation of AML1 and ETO genes through Cre/loxP-mediated recombination in the mouse.  EMBO Rep. 2000;  1 133-139
    Google Scholar
  • 110 Collins EC, Pannell R, Simpson EM, Forster A, Rabbitts TH. Inter-chromosomal recombination of Mll and Af9 genes mediated by cre-loxP in mouse development.  EMBO Rep. 2000;  1 127-132
    Google Scholar
  • 111 Sheils O. Molecular classification and biomarker discovery in papillary thyroid carcinoma.  Expert Rev Mol Diagn. 2005;  5 927-946
    Google Scholar

Correspondence

S-y. Cheng

Laboratory of Molecular Biology

National Cancer Institute

37 Convent Dr, Room 5128

Bethesda

20892-4264 MD

USA

Phone: +1/301/496 42 80

Fax: +1/301/402 13 44

Email: chengs@mail.nih.gov

      >