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Underexpression of PPAR gamma is associated with aneuploidy and lower differentiation of thyroid tumours of follicular origin

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Resumo:Peroxisome proliferator-activated receptor gamma (PPAR gamma) gene is a nuclear receptor that is involved in thyroid tumourigenesis. Recently, our group has shown that follicular carcinomas underexpressing PPAR gamma protein are more prone to develop distant metastases, to invade locally, to present poorly differentiated areas and to persist after surgery. Aneuploidy is also observed in some thyroid tumours, particularly in the more advanced cases. The aim of the present study was to investigate the association of PPAR gamma expression with the degree of differentiation and ploidy status of benign and malignant thyroid neoplasias. DNA cytometric studies, ploidy and S-phase fraction (SPF) determination, and quantitative RT-PCR analysis of molecular markers specific for thyroid follicular cells, namely Tg (thyroglobulin), TSHR (TSH receptor) and NIS (Na+/I- symporter) were compared between thyroid lesions with positive or negative PPAR gamma protein expression. We observed that PPAR gamma-negative tissues expressed lower levels of Tg mRNA [4.66x10(6) a.u. (arbitrary units) +/- 1.49x10(6)], and were more frequently aneuploid (36%), and presented higher SPF (3.1%+/- 0.4) than PPAR gamma-positive samples (Tg mRNA = 2.54x10(7) a.u. +/- 9.72 x 10(6). P=0.0006; aneuploidy=8%, P=0.0031; SPF=2.2%+/- 0.2, P=0.0430). A similar trend was also observed for TSHR and NIS mRNA, although not reaching statistical significance. This study showed that underexpression of PPAR gamma is associated with poor tumour differentiation, aneuploidy and higher cell proliferative activity. Therapies designed to modulate expression of PPAR gamma may have an impact on the growth of thyroid neoplasias.
Autores principais:Espadinha, C.
Outros Autores:Pinto, A.E.; Leite, Valeriano
Assunto:Ni+/I-symporterACTIVATED RECEPTOR-GAMMA TSH receptor FLOW-CYTOMETRY GROWTH-INHIBITION thyroglobulin PPAR gamma aneuploidy DNA-BINDING ACTIVITY thyroid GENE-EXPRESSION HUMAN BREAST-CANCER INDUCE APOPTOSIS HUMAN COLON-CANCER TERMINAL DIFFERENTIATION CARCINOMA-CELLS
Ano:2009
País:Portugal
Tipo de documento:artigo
Tipo de acesso:acesso aberto
Instituição associada:Universidade Nova de Lisboa
Idioma:inglês
Origem:Repositório Institucional da UNL

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