RESUMO
ß-Catenin is a central effector of the Wnt pathway and one of the players in Ca(+)-dependent cell-cell adhesion. While many wnts are present and expressed in vertebrates, only one ß-catenin exists in the majority of the organisms. One intriguing exception is zebrafish that carries two genes for ß-catenin. The maternal recessive mutation ichabod presents very low levels of ß-catenin2 that in turn affects dorsal axis formation, suggesting that ß-catenin1 is incapable to compensate for ß-catenin2 loss and raising the question of whether these two ß-catenins may have differential roles during early axis specification. Here we identify a specific antibody that can discriminate selectively for ß-catenin1. By confocal co-immunofluorescent analysis and low concentration gain-of-function experiments, we show that ß-catenin1 and 2 behave in similar modes in dorsal axis induction and cellular localization. Surprisingly, we also found that in the ich embryo the mRNAs of the components of ß-catenin regulatory pathway, including ß-catenin1, are more abundant than in the Wt embryo. Increased levels of ß-catenin1 are found at the membrane level but not in the nuclei till high stage. Finally, we present evidence that ß-catenin1 cannot revert the ich phenotype because it may be under the control of a GSK3ß-independent mechanism that required Axin's RGS domain function.
Assuntos
Proteína Axina/metabolismo , Mutação/genética , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/genética , Animais , Especificidade de Anticorpos , Proteína Axina/genética , Blástula/efeitos dos fármacos , Blástula/metabolismo , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Desenvolvimento Embrionário/efeitos dos fármacos , Desenvolvimento Embrionário/genética , Feminino , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Genes Dominantes , Imuno-Histoquímica , Cloreto de Lítio/farmacologia , Fenótipo , Estabilidade Proteica/efeitos dos fármacos , Transporte Proteico , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Transdução de Sinais/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/genética , Peixe-Zebra/embriologia , Proteínas de Peixe-Zebra/genética , beta Catenina/metabolismoRESUMO
BACKGROUND: Granular cell tumors (GCTs) or Abrikossoff's tumors are rare neoplasms known to originate from Schwann cells in the peripheral nervous system. These lesions are usually benign; malignancy only occurs in 1-2% of cases. Surgical resection is the traditional treatment method for GCTs, but it poses several risks and disadvantages related to the surgical incompatibility of the patient, the extended recovery time, and the chance of relapse. Cryoablation is becoming an increasingly favored method of treatment for tumors, both benign and malignant, due to its minimal invasiveness, natural analgesic properties, and ability to stimulate antitumor immunity. Cryoablation may contribute to the prevention of secondary and metastatic tumor growth in cases of malignancy by preserving tumor-associated antigen molecules for recognition by cell-mediated immunity. METHODS: This article describes a novel method for GCT treatment using cryoablation. This technique exposes tumor tissue to extreme cold temperatures, effectively destroying tumor cells by irreversibly compromising their plasma membranes. To our knowledge, this is the first report in the literature of cryoablative techniques being used for GCT. RESULTS: Cryoablation of this mass was successful with no complications. CT images during the procedure demonstrated circumferential coverage of the entire lesion with no injury to the surrounding tissues. CONCLUSION: Cryoablation can be used as an alternative to surgical intervention to treat malignant GCTs. This procedure is minimally invasive, less painful, and potentially effective in promoting antitumor immunity.