title: Components of the canonical and non-canonical Wnt pathways are not mis-expressed in pituitary tumors.
abstract: BACKGROUND
  Canonical and non-canonical Wnt pathways are involved in the genesis of multiple tumors; however, their role in pituitary tumorigenesis is mostly unknown.
  
  
  OBJECTIVE
  This study evaluated gene and protein expression of Wnt pathways in pituitary tumors and whether these expression correlate to clinical outcome.
  
  
  METHODS
  Genes of the WNT canonical pathway: activating ligands (WNT11, WNT4, WNT5A), binding inhibitors (DKK3, sFRP1), β-catenin (CTNNB1), β-catenin degradation complex (APC, AXIN1, GSK3β), inhibitor of β-catenin degradation complex (AKT1), sequester of β-catenin (CDH1), pathway effectors (TCF7, MAPK8, NFAT5), pathway mediators (DVL-1, DVL-2, DVL-3, PRICKLE, VANGL1), target genes (MYB, MYC, WISP2, SPRY1, TP53, CCND1); calcium dependent pathway (PLCB1, CAMK2A, PRKCA, CHP); and planar cell polarity pathway (PTK7, DAAM1, RHOA) were evaluated by QPCR, in 19 GH-, 18 ACTH-secreting, 21 non-secreting (NS) pituitary tumors, and 5 normal pituitaries. Also, the main effectors of canonical (β-catenin), planar cell polarity (JNK), and calcium dependent (NFAT5) Wnt pathways were evaluated by immunohistochemistry.
  
  
  RESULTS
  There are no differences in gene expression of canonical and non-canonical Wnt pathways between all studied subtypes of pituitary tumors and normal pituitaries, except for WISP2, which was over-expressed in ACTH-secreting tumors compared to normal pituitaries (4.8x; p = 0.02), NS pituitary tumors (7.7x; p = 0.004) and GH-secreting tumors (5.0x; p = 0.05). β-catenin, NFAT5 and JNK proteins showed no expression in normal pituitaries and in any of the pituitary tumor subtypes. Furthermore, no association of the studied gene or protein expression was observed with tumor size, recurrence, and progressive disease. The hierarchical clustering showed a regular pattern of genes of the canonical and non-canonical Wnt pathways randomly distributed throughout the dendrogram.
  
  
  CONCLUSIONS
  Our data reinforce previous reports suggesting no activation of canonical Wnt pathway in pituitary tumorigenesis. Moreover, we describe, for the first time, evidence that non-canonical Wnt pathways are also not mis-expressed in the pituitary tumors.
authors: Department of Internal Medicine, School of Medicine of Ribeirao Preto, University of Sao Paulo, Sao Paulo, Brazil.
authors: Leandro Machado
authors: LM
authors: Colli
authors: Fabiano
authors: F
authors: Saggioro
authors: Luciano Neder
authors: LN
authors: Serafini
authors: Renata Costa
authors: RC
authors: Camargo
authors: Helio Rubens
authors: HR
authors: Machado
authors: Ayrton Custodio
authors: AC
authors: Moreira
authors: Sonir R
authors: SR
authors: Antonini
authors: Margaret
authors: M
authors: de Castro
mesh_terms: D016000:Cluster Analysis; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000473:pathology; D060449:Wnt Signaling Pathway / Q000235:genetics*
chemical_list: D009363:Neoplasm Proteins
references: Nat Rev Endocrinol. 2011 May;7(5):257-66
references: 21423242
references: J Neurooncol. 2005 Jun;73(2):131-4
references: 15981102
references: Oncogene. 2009 Sep 10;28(36):3197-208
references: 19561643
references: Nat Rev Endocrinol. 2011 Feb;7(2):71-3
references: 21263436
references: Acta Neuropathol. 2010 May;119(5):631-9
references: 20131060
references: Acta Biochim Biophys Sin (Shanghai). 2008 Jul;40(7):577-94
references: 18604449
references: Int J Oncol. 2010 May;36(5):1129-36
references: 20372786
references: Proc Natl Acad Sci U S A. 2009 Nov 17;106(46):19473-8
references: 19901340
references: Birth Defects Res C Embryo Today. 2010 Dec;90(4):243-56
references: 21181886
references: Clin Endocrinol (Oxf). 2002 Oct;57(4):443-8
references: 12354125
references: Carcinogenesis. 2007 Jun;28(6):1178-87
references: 17227781
references: J Clin Endocrinol Metab. 2011 Oct;96(10):3106-14
references: 21849527
references: Am J Pathol. 2002 Dec;161(6):1997-2001
references: 12466115
references: Cancer. 2001 Jan 1;91(1):42-8
references: 11148558
references: Proc Natl Acad Sci U S A. 2006 Oct 17;103(42):15558-63
references: 17030811
references: Oncol Rep. 2005 Dec;14(6):1583-8
references: 16273260
references: Nat Rev Mol Cell Biol. 2009 Jul;10(7):468-77
references: 19536106
references: Horm Cancer. 2010 Aug;1(4):187-96
references: 21761366
references: Science. 2006 May 26;312(5777):1228-30
references: 16728643
references: Nucleic Acids Res. 2012 Jan;40(Database issue):D109-14
references: 22080510
references: Endocr Pathol. 2001 Summer;12(2):125-36
references: 11579678
references: J Cell Biol. 2003 May 26;161(4):769-77
references: 12771126
references: Biochem J. 2012 Oct 1;447(1):71-9
references: 22765757
references: Endocr Rev. 2011 Aug;32(4):453-71
references: 21493869
references: Acta Neuropathol. 2005 Jun;109(6):589-97
references: 15891929
references: Nature. 2000 Aug 3;406(6795):536-40
references: 10952317
references: Anticancer Res. 2007 Jul-Aug;27(4A):1769-76
references: 17649771
references: Cancer Res. 2008 Sep 15;68(18):7606-12
references: 18794149
references: Cancer Res. 2006 Nov 1;66(21):10439-48
references: 17079465
references: Exp Cell Res. 2011 Nov 15;317(19):2748-58
references: 21884696
references: PLoS Genet. 2012;8(3):e1002538
references: 22479189
references: Cell Cycle. 2008 Feb 1;7(3):297-303
references: 18235236
references: Pituitary. 2009;12(3):245-55
references: 18946739
references: Int J Cancer. 2007 Nov 1;121(9):1941-8
references: 17631641
references: Annu Rev Cell Dev Biol. 2004;20:781-810
references: 15473860
references: Endocr Pathol. 2008 Winter;19(4):261-73
references: 19034702
references: Pancreas. 2012 Jul;41(5):745-52
references: 22441145
references: Int J Oncol. 2002 Jun;20(6):1173-8
references: 12011995
references: Cancer Res. 1997 Dec 15;57(24):5446-51
references: 9407947
references: BMC Bioinformatics. 2009 Aug 27;10:268
references: 19712446
references: Cancer Lett. 2002 Sep 8;183(1):95-101
references: 12049819
references: Sci Transl Med. 2013 Jan 23;5(169):169ra10
references: 23345608
references: N Engl J Med. 2007 Apr 5;356(14):1432-7
references: 17409324
references: Proc Natl Acad Sci U S A. 2011 Jul 12;108(28):11482-7
references: 21636786