Components of the Canonical and Non-Canonical Wnt Pathways Are Not Mis-Expressed in Pituitary Tumors

Autor(es)

Colli, Leandro Machado ^[1] ; Saggioro, Fabiano ^[2] ; Serafini, Luciano Neder ^[2] ; Camargo, Renata Costa ^[1] ; Machado, Helio Rubens ^[3] ; Moreira, Ayrton Custodio ^[1] ; Antonini, Sonir R. ^[4] ; de Castro, Margaret ^[1]

Afiliação do(s) autor(es)

^[1] Univ Sao Paulo, Dept Internal Med, Sch Med Ribeirao Preto, Sao Paulo - Brazil

^[2] Univ Sao Paulo, Sch Med Ribeirao Preto, Dept Pathol, Sao Paulo - Brazil

^[3] Univ Sao Paulo, Dept Surg, Sch Med Ribeirao Preto, Sao Paulo - Brazil

^[4] Univ Sao Paulo, Dept Pediat, Sch Med Ribeirao Preto, Sao Paulo - Brazil

• Tipo de documento: Artigo Científico
• Fonte: PLoS One; v. 8, n. 4 APR 26 2013.
• Citações Web of Science: 15

Resumo

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), beta-catenin (CTNNB1), beta-catenin degradation complex (APC, AXIN1, GSK3 beta), inhibitor of beta-catenin degradation complex (AKT1), sequester of beta-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 (beta-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). beta-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 misexpressed in the pituitary tumors. (AU)

• Processo FAPESP: 07/58365-3 - Fisiopatologia e etiopatogenia molecular de doenças relacionadas aos eixos corticotrófico, somatotrófico e neurohipofisário
• Beneficiário: Margaret de Castro
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 10/01286-7 - Análise da via da beta-catenina em tumores hipofisários não secretores e secretores de GH e ACTH
• Beneficiário: Leandro Machado Colli
• Modalidade de apoio: Bolsas no Brasil - Doutorado Direto