13 research outputs found
Nitrogênio e potássio no crescimento de mudas de pitaia [Hylocereus undatus (Haw.) Britton & Rose]
Atividade antifúngica de óleos essenciais de espécies de Piper sobre Crinipellis perniciosa, Phytophthora palmivora e Phytophthora capsici
Efeito do óleo de Piper aduncum no controle em pós-colheita de Colletotricum musae em banana
The RET p.G533C Mutation Confers Predisposition to Multiple Endocrine Neoplasia Type 2A in a Brazilian Kindred and Is Able to Induce a Malignant Phenotype in Vitro and in Vivo
Background: We have previously described a p.G533C substitution in the rearranged during transfection (RET) oncogene in a large family with medullary thyroid carcinoma. Here, we explore the functional transforming potential of RET p.G533C mutation.Methods: Plasmids expressing RET mutants (p.G533C and p.C634Y) and RET wild type were stable transfected into a rat thyroid cell line (PCCL3). Biological and biochemical effects of RET p.G533C were investigated both in vitro and in vivo. Moreover, we report the first case of pheochromocytoma among the RET p.G533C-carriers in this Brazilian family and explore the RET mutational status in DNA isolated from pheochromocytoma.Results: Ectopic expression of RET p.G533C and p.C634Y activates RET/MAPK/ERK pathway at similar levels and significantly increased cell proliferation, compared with RET wild type. We additionally show that p.G533C increased cell viability, anchorage-independent growth, and micronuclei formation while reducing apoptosis, hallmarks of the malignant phenotype. RET p.G533C down-regulates the expression of thyroid specific genes in PCCL3. Moreover, RET p.G533C-expressing cells were able to induce liver metastasis in nude mice. Finally, we described two novel RET variants (G548V and S556T) in the DNA isolated from pheochromocytoma while they were absent in the DNA isolated from blood.Conclusions: Our in vitro and in vivo analysis indicates that this mutation confers a malignant phenotype to PCCL3 cells. These findings, in association with the report of first case of pheochromocytoma in the Brazilian kindred, suggest that this noncysteine mutation may be more aggressive than was initially considered.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Universidade Federal de São Paulo, Div Genet, Genet Bases Thyroid Tumors Lab, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Div Endocrinol, Mol Endocrinol Lab, BR-04039032 São Paulo, BrazilUniv Fed Minas Gerais, Div Endocrinol, Belo Horizonte, MG, BrazilUniversidade Federal de São Paulo, Div Genet, Genet Bases Thyroid Tumors Lab, BR-04039032 São Paulo, BrazilUniversidade Federal de São Paulo, Div Endocrinol, Mol Endocrinol Lab, BR-04039032 São Paulo, BrazilFAPESP: 05/60330-8FAPESP: 06/60402-1FAPESP: 09/11257-7Web of Scienc