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. 2013 Apr 26;8(4):e62424.
doi: 10.1371/journal.pone.0062424. Print 2013.

Components of the canonical and non-canonical Wnt pathways are not mis-expressed in pituitary tumors

Leandro Machado Colli  1 , Fabiano Saggioro, Luciano Neder Serafini, Renata Costa Camargo, Helio Rubens Machado, Ayrton Custodio Moreira, Sonir R Antonini, Margaret de Castro
Affiliations

Components of the canonical and non-canonical Wnt pathways are not mis-expressed in pituitary tumors

Leandro Machado Colli et al. PLoS One. .

Abstract

Introduction: 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.

Materials and 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.

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Conflict of interest statement

Competing Interests: The authors have declared that no competing interests exist.

Figures

Figure 1
Figure 1. Hierarchical clustering for canonical and non-canonical Wnt pathway genes in normal pituitary and in different subtypes of the pituitary tumors.
HN: normal pituitary; ACTH: ACTH-secreting pituitary tumor; GH: GH-secreting pituitary tumor; NS: non-secreting pituitary tumor.
Figure 2
Figure 2. Immunocytochemistry for β-catenin, JNK, and NFAT5 in normal pituitaries, ACTH-secreting pituitary tumor, GH-secreting pituitary tumor, and non-secreting pituitary tumor (x40).
ACTH and GH immune positivity are shown in the region of the tumor sample immunostained for β-catenin, JNK and NFAT. Craniopharyngioma tissue and two positive samples from GH-secreting pituitary tumors were used as positive controls for β-catenin, NFAT5, and JNK antibodies, respectively.
See this image and copyright information in PMC

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This work was supported by Sao Paulo Research Foundation (FAPESP grant numbers 2010/01286-7 and 2007/58365-3) and Brazilian National Council for Research and Development (CNPq grant number 2008/3003867). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.