Please use this identifier to cite or link to this item: https://repositorio.unifesp.br/handle/11600/34022
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dc.contributor.authorOliveira, Mariana N. L. [UNIFESP]
dc.contributor.authorHemerly, Jefferson P. [UNIFESP]
dc.contributor.authorBastos, Andre U. [UNIFESP]
dc.contributor.authorTamanaha, Rosana [UNIFESP]
dc.contributor.authorLatini, Flavia R. M. [UNIFESP]
dc.contributor.authorCamacho, Cleber P. [UNIFESP]
dc.contributor.authorImpellizzeri, Anelise
dc.contributor.authorMaciel, Rui M. B. [UNIFESP]
dc.contributor.authorCerutti, Janete M. [UNIFESP]
dc.date.accessioned2016-01-24T14:17:11Z-
dc.date.available2016-01-24T14:17:11Z-
dc.date.issued2011-09-01
dc.identifierhttp://dx.doi.org/10.1089/thy.2010.0190
dc.identifier.citationThyroid. New Rochelle: Mary Ann Liebert Inc, v. 21, n. 9, p. 975-985, 2011.
dc.identifier.issn1050-7256
dc.identifier.urihttp://repositorio.unifesp.br/handle/11600/34022-
dc.description.abstractBackground: 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.en
dc.description.sponsorshipFundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.format.extent975-985
dc.language.isoeng
dc.publisherMary Ann Liebert Inc
dc.relation.ispartofThyroid
dc.rightsAcesso restrito
dc.titleThe 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 Vivoen
dc.typeArtigo
dc.contributor.institutionUniversidade Federal de São Paulo (UNIFESP)
dc.contributor.institutionUniversidade Federal de Minas Gerais (UFMG)
dc.description.affiliationUniversidade Federal de São Paulo, Div Genet, Genet Bases Thyroid Tumors Lab, BR-04039032 São Paulo, Brazil
dc.description.affiliationUniversidade Federal de São Paulo, Div Endocrinol, Mol Endocrinol Lab, BR-04039032 São Paulo, Brazil
dc.description.affiliationUniv Fed Minas Gerais, Div Endocrinol, Belo Horizonte, MG, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Div Genet, Genet Bases Thyroid Tumors Lab, BR-04039032 São Paulo, Brazil
dc.description.affiliationUnifespUniversidade Federal de São Paulo, Div Endocrinol, Mol Endocrinol Lab, BR-04039032 São Paulo, Brazil
dc.description.sponsorshipIDFAPESP: 05/60330-8
dc.description.sponsorshipIDFAPESP: 06/60402-1
dc.description.sponsorshipIDFAPESP: 09/11257-7
dc.identifier.doi10.1089/thy.2010.0190
dc.description.sourceWeb of Science
dc.identifier.wosWOS:000294768800006
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