The role of the PAX8/PPARγ fusion oncogene in the pathogenesis of follicular thyroid cancer

Molecular and Cellular Endocrinology

Volumn 321, Issue 1, 2010, Pages 50-56

  Eberhardt, Norman L ^a   Grebe, Stefan K G ^a   McIver, Bryan ^a   Reddi, Honey V ^a  

^a MAYO CLINIC   (United States)

Author keywords

Follicular thyroid cancer; PAX8; PAX8 PPAR fusion oncogene; PPAR

Indexed keywords

CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN; CYCLIC AMP RESPONSIVE ELEMENT BINDING PROTEIN 3 LIKE 2; PEROXISOME PROLIFERATOR ACTIVATED RECEPTOR GAMMA; TRANSCRIPTION FACTOR PAX8; UNCLASSIFIED DRUG; ONCOPROTEIN; PAIRED BOX TRANSCRIPTION FACTOR; PAX8 PPARGAMMA FUSION PROTEIN, HUMAN; PAX8-PPARGAMMA FUSION PROTEIN, HUMAN;

CANCER INCIDENCE; CARCINOGENESIS; CELL DIFFERENTIATION; CHROMOSOME 2Q; CHROMOSOME 3P; CHROMOSOME REARRANGEMENT; CHROMOSOME TRANSLOCATION 2; CHROMOSOME TRANSLOCATION 3; GENETIC TRANSFECTION; HEREDITY; NONHUMAN; ONCOGENE; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PROTEIN INTERACTION; REVIEW; THYROID CARCINOGENESIS; THYROID FOLLICULAR CARCINOMA; ADENOCARCINOMA; ANIMAL; CHROMOSOME ABERRATION; GENETICS; HUMAN; METABOLISM; THYROID TUMOR;

ADENOCARCINOMA, FOLLICULAR; ANIMALS; CHROMOSOME ABERRATIONS; HUMANS; ONCOGENE PROTEINS, FUSION; PAIRED BOX TRANSCRIPTION FACTORS; PPAR GAMMA; THYROID NEOPLASMS;

EID: 77950922596     PISSN: 03037207     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.mce.2009.10.013     Document Type: Review

References (65)

1. Au A.Y., McBride C., Wilhelm K.G., Koenig R.J., Speller B., Cheung L., Messina M., Wentworth J., Tasevski V., Learoyd D., Robinson B.G., Clifton-Bligh R.J. PAX8-peroxisome proliferator-activated receptor gamma (PPARgamma) disrupts normal PAX8 or PPARgamma transcriptional function and stimulates follicular thyroid cell growth. Endocrinology 2006, 147:367-376.
2. Banito A., Pinto A.E., Espadinha C., Marques A.R., Leite V. Aneuploidy and RAS mutations are mutually exclusive events in the development of well-differentiated thyroid follicular tumours. Clin. Endocrinol. 2007, 67:706-711.
3. Cameselle-Teijeiro J., Pardal F., Eloy C., Ruiz-Ponte C., Celestino R., Castro P., Soares P., Sobrinho-Simoes M. Follicular thyroid carcinoma with an unusual glomeruloid pattern of growth. Hum. Pathol. 2008, 39:1540-1547.
4. Castro P., Rebocho A.P., Soares R.J., Magalhaes J., Roque L., Trovisco V., Vieira de Castro I., Cardoso-de-Oliveira M., Fonseca E., Soares P., Sobrinho-Simoes M. PAX8-PPARgamma rearrangement is frequently detected in the follicular variant of papillary thyroid carcinoma. J. Clin. Endocrinol. Metab. 2006, 91:213-220.
5. Copland J.A., Marlow L.A., Kurakata S., Fujiwara K., Wong A.K., Kreinest P.A., Williams S.F., Haugen B.R., Klopper J.P., Smallridge R.C. Novel high-affinity PPARgamma agonist alone and in combination with paclitaxel inhibits human anaplastic thyroid carcinoma tumor growth via p21WAF1/CIP1. Oncogene 2006, 25:2304-2317.
6. Davies L., Welch H.G. Increasing incidence of thyroid cancer in the United States, 1973-2002. JAMA 2006, 295:2164-2167.
7. Di Cristofaro J., Silvy M., Lanteaume A., Marcy M., Carayon P., De Micco C. Expression of tpo mRNA in thyroid tumors: quantitative PCR analysis and correlation with alterations of ret, Braf, ras and pax8 genes. Endocr. Relat. Cancer 2006, 13:485-495.
8. Drieschner N., Belge G., Rippe V., Meiboom M., Loeschke S., Bullerdiek J. Evidence for a 3p25 breakpoint hot spot region in thyroid tumors of follicular origin. Thyroid 2006, 16:1091-1096.
9. Espadinha C., Cavaco B.M., Leite V. PAX8PPARgamma stimulates cell viability and modulates expression of thyroid-specific genes in a human thyroid cell line. Thyroid 2007, 17:497-509.
10. Fajas L., Debril M.B., Auwerx J. Peroxisome proliferator-activated receptor-gamma: from adipogenesis to carcinogenesis. J. Mol. Endocrinol. 2001, 27:1-9.
11. Fajas L., Debril M.B., Auwerx J. PPAR gamma: an essential role in metabolic control. Nutr. Metab. Cardiovas. Dis. 2001, 11:64-69.
12. Foukakis T., Au A.Y., Wallin G., Geli J., Forsberg L., Clifton-Bligh R., Robinson B.G., Lui W.O., Zedenius J., Larsson C. The Ras effector NORE1A is suppressed in follicular thyroid carcinomas with a PAX8-PPARgamma fusion. J. Clin. Endocrinol. Metab. 2006, 91:1143-1149.
13. French C.A., Alexander E.K., Cibas E.S., Nose V., Laguette J., Faquin W., Garber J., Moore F., Fletcher J.A., Larsen P.R., Kroll T.G. Genetic and biological subgroups of low-stage follicular thyroid cancer. Am. J. Pathol. 2003, 162:1053-1060.
14. Giordano T.J., Au A.Y., Kuick R., Thomas D.G., Rhodes D.R., Wilhelm K.G., Vinco M., Misek D.E., Sanders D., Zhu Z., Ciampi R., Hanash S., Chinnaiyan A., Clifton-Bligh R.J., Robinson B.G., Nikiforov Y.E., Koenig R.J. Delineation, functional validation, and bioinformatic evaluation of gene expression in thyroid follicular carcinomas with the PAX8-PPARg translocation. Clin. Cancer Res. 2006, 12:1983-1993.
15. Grebe S.K., Hay I.D. Follicular thyroid cancer. Endocrinol. Metab. Clin. North Am. 1995, 24:761-801.
16. Grebe S.K., McIver B., Hay I.D., Wu P.S., Maciel L.M., Drabkin H.A., Goellner J.R., Grant C.S., Jenkins R.B., Eberhardt N.L. Frequent loss of heterozygosity on chromosomes 3p and 17p without VHL or p53 mutations suggests involvement of unidentified tumor suppressor genes in follicular thyroid carcinoma. J. Clin. Endocrinol. Metab. 1997, 82:3684-3691.
17. Greenlee R.T., Murray T., Bolden S., Wingo P.A. Cancer statistics, 2000. CA Cancer J. Clin. 2000, 50:7-33.
18. Gregory Powell J., Wang X., Allard B.L., Sahin M., Wang X.L., Hay I.D., Hiddinga H.J., Deshpande S.S., Kroll T.G., Grebe S.K., Eberhardt N.L., McIver B. The PAX8/PPARgamma fusion oncoprotein transforms immortalized human thyrocytes through a mechanism probably involving wild-type PPARgamma inhibition. Oncogene 2004, 23:3634-3641.
19. Hou P., Liu D., Shan Y., Hu S., Studeman K., Condouris S., Wang Y., Trink A., El-Naggar A.K., Tallini G., Vasko V., Xing M. Genetic alterations and their relationship in the phosphatidylinositol 3-kinase/Akt pathway in thyroid cancer. Clin. Cancer Res. 2007, 13:1161-1170.
20. Jemal A., Siegel R., Ward E., Hao Y., Xu J., Murray T., Thun M.J. Cancer statistics, 2008. CA Cancer J. Clin. 2008, 58:71-96.
21. Jhiang S.M., Sagartz J.E., Tong Q., Parker-Thornburg J., Capen C.C., Cho J.Y., Xing S., Ledent C. Targeted expression of the ret/PTC1 oncogene induces papillary thyroid carcinomas. Endocrinology 1996, 137:375-378.
22. Jhiang S.M., Cho J.Y., Furminger T.L., Sagartz J.E., Tong Q., Capen C.C., Mazzaferri E.L. Thyroid carcinomas in RET/PTC transgenic mice. Recent Result Cancer Res. 1998, 154:265-270.
23. Jhiang S.M. The RET proto-oncogene in human cancers. Oncogene 2000, 19:5590-5597.
24. Kim C.S., Vasko V.V., Kato Y., Kruhlak M., Saji M., Cheng S.Y., Ringel M.D. AKT activation promotes metastasis in a mouse model of follicular thyroid carcinoma. Endocrinology 2005, 146:4456-4463.
25. Kimura E.T., Nikiforova M.N., Zhu Z., Knauf J.A., Nikiforov Y.E., Fagin J.A. 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.
26. Kishida K., Shimomura I., Nishizawa H., Maeda N., Kuriyama H., Kondo H., Matsuda M., Nagaretani H., Ouchi N., Hotta K., Kihara S., Kadowaki T., Funahashi T., Matsuzawa Y. Enhancement of the aquaporin adipose gene expression by a peroxisome proliferator-activated receptor gamma. J. Biol. Chem. 2001, 276:48572-48579.
27. Knauf J.A., Kuroda H., Basu S., Fagin J.A. RET/PTC-induced dedifferentiation of thyroid cells is mediated through Y1062 signaling through SHC-RAS-MAP kinase. Oncogene 2003, 22:4406-4412.
28. Knauf J.A., Ma X., Smith E.P., Zhang L., Mitsutake N., Liao X.H., Refetoff S., Nikiforov Y.E., Fagin J.A. Targeted expression of BRAFV600E in thyroid cells of transgenic mice results in papillary thyroid cancers that undergo dedifferentiation. Cancer Res. 2005, 65:4238-4245.
29. Krishnan A., Nair S.A., Pillai M.R. Biology of PPAR gamma in cancer: a critical review on existing lacunae. Curr. Mol. Med. 2007, 7:532-540.
30. Kroll T.G., Sarraf P., Pecciarini L., Chen C.J., Mueller E., Spiegelman B.M., Fletcher J.A. PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma. Science 2000, 289:1357-1360.
31. Le H.N., Norton J.A. Perspective on RET proto-oncogene and thyroid cancer. Cancer J. 2000, 6:50-57.
32. Leboeuf R., Baumgartner J.E., Benezra M., Malaguarnera R., Solit D., Pratilas C.A., Rosen N., Knauf J.A., Fagin J.A. BRAFV600E mutation is associated with preferential sensitivity to mitogen-activated protein kinase kinase inhibition in thyroid cancer cell lines. J. Clin. Endocrinol. Metab. 2008, 93:2194-2201.
33. Lui W.O., Zeng L., Rehrmann V., Deshpande S., Tretiakova M., Kaplan E.L., Leibiger I., Leibiger B., Enberg U., Hoog A., Larsson C., Kroll T.G. CREB3L2-PPARgamma fusion mutation identifies a thyroid signaling pathway regulated by intramembrane proteolysis. Cancer Res. 2008, 68:7156-7164.
34. Macchia P.E., Lapi P., Krude H., Pirro M.T., Missero C., Chiovato L., Souabni A., Baserga M., Tassi V., Pinchera A., Fenzi G., Gruters A., Busslinger M., Di Lauro R. PAX8 mutations associated with congenital hypothyroidism caused by thyroid dysgenesis. Nat. Genet. 1998, 19:83-86.
35. Marques A.R., Espadinha C., Catarino A.L., Moniz S., Pereira T., Sobrinho L.G., Leite V. Expression of PAX8-PPAR gamma 1 rearrangements in both follicular thyroid carcinomas and adenomas. J. Clin. Endocrinol. Metab. 2002, 87:3947-3952.
36. Masugi J., Tamori Y., Kasuga M. Inhibition of adipogenesis by a COOH-terminally truncated mutant of PPARgamma2 in 3T3-L1 cells. Biochem. Biophys. Res. Commun. 1999, 264:93-99.
37. Matsuyama M., Yoshimura R. A novel approach to anticancer therapies: peroxisome proliferator activator-receptor-gamma as a new target therapy in the treatment of human urological cancer. Endocr. Metab. Immune Disord. Drug Targets 2009, 9:76-83.
38. Melillo R.M., Castellone M.D., Guarino V., De Falco V., Cirafici A.M., Salvatore G., Caiazzo F., Basolo F., Giannini R., Kruhoffer M., Orntoft T., Fusco A., Santoro M. The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells. J. Clin. Invest. 2005, 115:1068-1081.
39. Michalik L., Auwerx J., Berger J.P., Chatterjee V.K., Glass C.K., Gonzalez F.J., Grimaldi P.A., Kadowaki T., Lazar M.A., O'Rahilly S., Palmer C.N., Plutzky J., Reddy J.K., Spiegelman B.M., Staels B., Wahli W. International Union of Pharmacology. LXI. Peroxisome proliferator-activated receptors. Pharmacol. Rev. 2006, 58:726-741.
40. Motti M.L., De Marco C., Califano D., De Gisi S., Malanga D., Troncone G., Persico A., Losito S., Fabiani F., Santoro M., Chiappetta G., Fusco A., Viglietto G. Loss of p27 expression through RAS-->BRAF-->MAP kinase-dependent pathway in human thyroid carcinomas. Cell Cycle 2007, 6:2817-2825.
41. Nikiforova M.N., Stringer J.R., Blough R., Medvedovic M., Fagin J.A., Nikiforov Y.E. Proximity of chromosomal loci that participate in radiation-induced rearrangements in human cells. Science 2000, 290:138-141.
42. Nikiforova M.N., Biddinger P.W., Caudill C.M., Kroll T.G., Nikiforov Y.E. PAX8-PPARgamma rearrangement in thyroid tumors: RT-PCR and immunohistochemical analyses. Am. J. Surg. Pathol. 2002, 26:1016-1023.
43. Nikiforova M.N., Kimura E.T., Gandhi M., Biddinger P.W., Knauf J.A., Basolo F., Zhu Z., Giannini R., Salvatore G., Fusco A., Santoro M., Fagin J.A., Nikiforov Y.E. BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J. Clin. Endocrinol. Metab. 2003, 88:5399-5404.
44. Nikiforova M.N., Lynch R.A., Biddinger P.W., Alexander E.K., Dorn G.W., Tallini G., Kroll T.G., Nikiforov Y.E. 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.
45. Ouyang B., Knauf J.A., Smith E.P., Zhang L., Ramsey T., Yusuff N., Batt D., Fagin J.A. Inhibitors of Raf kinase activity block growth of thyroid cancer cells with RET/PTC or BRAF mutations in vitro and in vivo. Clin. Cancer Res. 2006, 12:1785-1793.
46. Paes J.E., Ringel M.D. Dysregulation of the phosphatidylinositol 3-kinase pathway in thyroid neoplasia. Endocrinol. Metab. Clin. North Am. 2008, 37:375-387.
47. Pasca di Magliano M., Di Lauro R., Zannini M. Pax8 has a key role in thyroid cell differentiation. Proc. Natl. Acad. Sci. U.S.A. 2000, 97:13144-13149.
48. Placzkowski K.A., Reddi H.V., Grebe S.K.G., Eberhardt N.L., McIver B. The role of the PAX8/PPAR-gamma fusion oncogene in thyroid cancer. PPAR Research 2008 2008, Article ID 672829, http://www.hindawi.com/.
49. Powell D.J., Russell J., Nibu K., Li G., Rhee E., Liao M., Goldstein M., Keane W.M., Santoro M., Fusco A., Rothstein J.L. The RET/PTC3 oncogene: metastatic solid-type papillary carcinomas in murine thyroids. Cancer Res. 1998, 58:5523-5528.
50. Rieusset J., Auwerx J., Vidal H. Regulation of gene expression by activation of the peroxisome proliferator-activated receptor gamma with rosiglitazone (BRL 49653) in human adipocytes. Biochem. Biophys. Res. Commun. 1999, 265:265-271.
51. Ringel M.D., Hayre N., Saito J., Saunier B., Schuppert F., Burch H., Bernet V., Burman K.D., Kohn L.D., Saji M. Overexpression and overactivation of Akt in thyroid carcinoma. Cancer Res. 2001, 61:6105-6111.
52. Rumi M.A., Ishihara S., Kazumori H., Kadowaki Y., Kinoshita Y. Can PPAR gamma ligands be used in cancer therapy?. Curr. Med. Chem. Anticancer Agents 2004, 4:465-477.
53. Saito J., Kohn A.D., Roth R.A., Noguchi Y., Tatsumo I., Hirai A., Suzuki K., Kohn L.D., Saji M., Ringel M.D. Regulation of FRTL-5 thyroid cell growth by phosphatidylinositol (OH) 3 kinase-dependent Akt-mediated signaling. Thyroid 2001, 11:339-351.
54. Santarpia L., El-Naggar A.K., Cote G.J., Myers J.N., Sherman S.I. Phosphatidylinositol 3-kinase/akt and ras/raf-mitogen-activated protein kinase pathway mutations in anaplastic thyroid cancer. J. Clin. Endocrinol. Metab. 2008, 93:278-284.
55. Santarpia L., Sherman S.I., Marabotti A., Clayman G.L., El-Naggar A.K. Detection and molecular characterization of a novel BRAF activated domain mutation in follicular variant of papillary thyroid carcinoma. Hum. Pathol. 2009, 40:827-833.
56. Schoonjans K., Martin G., Staels B., Auwerx J. Peroxisome proliferator-activated receptors, orphans with ligands and functions. Curr. Opin. Lipidol. 1997, 8:159-166.
57. Shen W.T., Chung W.Y. Treatment of thyroid cancer with histone deacetylase inhibitors and peroxisome proliferator-activated receptor-gamma agonists. Thyroid 2005, 15:594-599.
58. Tallini G., Asa S.L. RET oncogene activation in papillary thyroid carcinoma. Adv. Anat. Pathol. 2001, 8:345-354.
59. Wang T., Xu J., Yu X., Yang R., Han Z.C. Peroxisome proliferator-activated receptor gamma in malignant diseases. Crit. Rev. Oncol. Hematol. 2006, 58:1-14.
60. Ward E.M., Thun M.J., Hannan L.M., Jemal A. Interpreting cancer trends. Ann. N. Y. Acad. Sci. 2006, 1076:29-53.
61. Ward L.S., Brenta G., Medvedovic M., Fagin J.A. Studies of allelic loss in thyroid tumors reveal major differences in chromosomal instability between papillary and follicular carcinomas. J. Clin. Endocrinol. Metab. 1998, 83:525-530.
62. Wu X., Groves F.D., McLaughlin C.C., Jemal A., Martin J., Chen V.W. Cancer incidence patterns among adolescents and young adults in the United States. Cancer Causes Control 2005, 16:309-320.
63. Yin Y., Yuan H., Zeng X., Kopelovich L., Glazer R.I. Inhibition of peroxisome proliferator-activated receptor gamma increases estrogen receptor-dependent tumor specification. Cancer Res. 2009, 69:687-694.
64. Zeng L., Geng Y., Tretiakova M., Yu X., Sicinski P., Kroll T.G. Peroxisome proliferator-activated receptor-delta induces cell proliferation by a cyclin E1-dependent mechanism and is up-regulated in thyroid tumors. Cancer Res. 2008, 68:6578-6586.
65. Zhu Z., Gandhi M., Nikiforova M.N., Fischer A.H., Nikiforov Y.E. Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations. Am. J. Clin. Pathol. 2003, 120:71-77.