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Doctoral Thesis
DOI
https://doi.org/10.11606/T.42.2008.tde-06102008-160716
Document
Author
Full name
Luciane Martins
Institute/School/College
Knowledge Area
Date of Defense
Published
São Paulo, 2008
Supervisor
Committee
Kimura, Edna Teruko (President)
Ferro, Emer Suavinho
Martins, Joao Roberto Maciel
Nogueira, Célia Regina
Santelli, Glaucia Maria Machado
Title in Portuguese
A galectina-3 na fisiologia e no câncer de tiróide: identificação de SNPs no gene LGALS3 e estudo funcional de galectina-3 in vitro e in vivo
Keywords in Portuguese
Câncer de tireóide
Ciclo celular e apoptose
Galectina-3
Interferência de RNA
Polimorfismo de um único nucleotídeo
Sinalização celular
Abstract in Portuguese
Neste estudo, investigamos o envolvimento de galectina-3 na fisiologia e no câncer de tiróide usando vários modelos biológicos e metodologias. Observamos que o gene LGALS3 apresenta um SNP no códon 98, mas não observamos correlação entre os genótipos deste SNP e fenótipo de câncer de tiróide. Na linhagem de tiróide de rato PCCl3, mostramos que a indução da expressão do oncogene RET/PTC promove o aumento da expressão de galectina-3, no entanto, a expressão de galectina-3, por si só, não confere vantagem de proliferação à célula. Por outro lado, na linhagem de carcinoma papilífero de tiróide TPC-1, a galectina-3 contribui para a sobrevivência da célula tumoral e progressão do ciclo celular, aumentando a expressão de c-Myc, diminuindo a expressão de p21 e caspase-3, e favorecendo a ativação de importantes vias envolvidas no controle do ciclo celular. Além disto, em modelos in vivo e in vitro, a galectina-3 interferiu na função e diferenciação da célula folicular tiroidiana, exercendo um papel indireto na regulação da expressão da tireoglobulina e atividade de TTF-1.
Title in English
Galectin-3 in thyroid physiology and cancer: identification of SNPs in the LGALS3 gene and functional study of galectin-3 in vitro and in vivo.
Keywords in English
Cell cycle and apoptosis
Cell signaling
Galectin-3
RNA interference
Single nucleotide polymorphism (SNP)
Thyroid cancer
Abstract in English
In this study, we investigate the involvement of galectin-3 in thyroid physiology and cancer using several biological models and methodologies. We observed that LGALS3 gene presents a SNP in codon 98, but no correlation between the genotype and the phenotype of benign or malignant thyroid tumor was observed. In the rat thyroid cell line PCCl3, we showed that the conditional induction of RET/PTC oncogene expression promotes the increase of galectin-3 expression, however, galectin-3 expression itself did not confer a proliferative advantage to cell. On the other hand, in papillary thyroid carcinoma cell line TPC-1 the galectin-3 contributes to tumor cell survival and cell cycle progression, increasing c-Myc expression, decreasing p21 and caspase-3 expression and cooperating to activation of important signaling pathways which are involved in the cell cycle control. In addition, in vitro and in vivo models the galectin-3 interferes in the differentiation and function of thyroid follicular cell, playing an indirect role in the regulation of thyroglobulin expression and TTF-1 activity.
 
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Publishing Date
2008-10-08
 
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