p27 variant and corticotropinoma susceptibility: a genetic and in vitro study

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dc.contributor.author Sekiya, Tomoko
dc.contributor.author Bronstein, Marcello D.
dc.contributor.author Benfini, Katiuscia
dc.contributor.author Longuini, Viviane C.
dc.contributor.author Jallad, Raquel S.
dc.contributor.author Machado, Marcio C.
dc.contributor.author Goncalves, Tatiana D.
dc.contributor.author Osaki, Luciana H.
dc.contributor.author Higashi, Leonardo
dc.contributor.author Viana-Junior, Jose [UNIFESP]
dc.contributor.author Kater, Claudio
dc.contributor.author Lee, Misu
dc.contributor.author Molatore, Sara
dc.contributor.author Francisco, Guilherme
dc.contributor.author Chammas, Roger
dc.contributor.author Naslavsky, Michel S.
dc.contributor.author Schlesinger, David
dc.contributor.author Gama, Patricia
dc.contributor.author Duarte, Yeda A. O.
dc.contributor.author Lebrao, Maria Lucia
dc.contributor.author Zatz, Mayana
dc.contributor.author Meirelles, Osorio
dc.contributor.author Liberman, Bernardo
dc.contributor.author Fragoso, Maria Candida B. V.
dc.contributor.author Toledo, Sergio P. A.
dc.contributor.author Pellegata, Natalia S.
dc.contributor.author Toledo, Rodrigo A.
dc.date.accessioned 2016-01-24T14:37:20Z
dc.date.available 2016-01-24T14:37:20Z
dc.date.issued 2014-06-01
dc.identifier http://dx.doi.org/10.1530/ERC-13-0486
dc.identifier.citation Endocrine-related Cancer. Bristol: Bioscientifica Ltd, v. 21, n. 3, p. 395-404, 2014.
dc.identifier.issn 1351-0088
dc.identifier.uri http://repositorio.unifesp.br/handle/11600/37807
dc.description.abstract Germline mutations in p27(kip1) are associated with increased susceptibility to multiple endocrine neoplasias (MEN) both in rats and humans; however, the potential role of common polymorphisms of this gene in endocrine tumor susceptibility and tumorigenesis remains mostly unrecognized. To assess the risk associated with polymorphism rs2066827 (p27-V109G), we genotyped a large cohort of Brazilian patients with sporadic endocrine tumors (pituitary adenomas, n=252; pheochromocytomas, n=125; medullary thyroid carcinoma, n=51; and parathyroid adenomas, n=19) and 885 population- matched healthy controls and determined the odds ratios and 95% CIs. Significant associations were found for the group of patients with pituitary adenomas (P=0.01), particularly for those with ACTH-secreting pituitary adenomas (P=0.005). in contrast, no association was found with GH- secreting pituitary tumors alone or with the sporadic counterpart of MEN2- component neoplasias. Our in vitro analyses revealed increased colony formation and cell growth rate for an AtT20 corticotropin mouse cell line overexpressing the p27- V109G variant compared with cells transfected with the WT p27. However, the genotypic effects in genetic and in vitro approaches were divergent. in accordance with our genetic data showing specificity for ACTH- secreting pituitary tissues, the overexpression of p27-V109G in a GH3 somatotropin rat cell line resulted in no difference compared with the WT. Pituitary tumors are one of the major clinical components of syndromes associated with the p27 pathogenic mutations MENX and MEN4. Our genetic and in vitro data indicate that the common polymorphism rs2066827 may play a role in corticotropinoma susceptibility and tumorigenesis through a molecular mechanism not fully understood thus far. en
dc.description.sponsorship Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
dc.description.sponsorship Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
dc.description.sponsorship Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
dc.format.extent 395-404
dc.language.iso eng
dc.publisher Bioscientifica Ltd
dc.relation.ispartof Endocrine-related Cancer
dc.rights Acesso aberto
dc.subject endocrine tumor en
dc.subject p27 en
dc.subject corticotropinoma en
dc.subject pituitary tumor en
dc.title p27 variant and corticotropinoma susceptibility: a genetic and in vitro study en
dc.type Artigo
dc.contributor.institution Universidade de São Paulo (USP)
dc.contributor.institution Santa Casa Hosp
dc.contributor.institution Brigadeiro Hosp
dc.contributor.institution Universidade Federal de São Paulo (UNIFESP)
dc.contributor.institution Inst Israelita Ensino & Pesquisa Albert Einstein
dc.contributor.institution NIA
dc.contributor.institution Helmholtz Zentrum Munchen
dc.description.affiliation Univ São Paulo, Hosp Clin, Sch Med, Endocrine Genet Unit LIM 25, São Paulo, Brazil
dc.description.affiliation Univ São Paulo, Hosp Clin, Sch Med, Neuroendocrinol Unit, São Paulo, Brazil
dc.description.affiliation Univ São Paulo, Hosp Clin, Sch Med, Adrenal Unit LIM 42, São Paulo, Brazil
dc.description.affiliation Univ São Paulo, Hosp Clin, Sch Med, Expt Oncol Lab LIM 24, São Paulo, Brazil
dc.description.affiliation Univ São Paulo, Sch Nursing, São Paulo, Brazil
dc.description.affiliation Univ São Paulo, Sch Publ Hlth, São Paulo, Brazil
dc.description.affiliation Santa Casa Hosp, Div Endocrinol, São Paulo, Brazil
dc.description.affiliation Brigadeiro Hosp, São Paulo, Brazil
dc.description.affiliation Universidade Federal de São Paulo, São Paulo, Brazil
dc.description.affiliation Univ São Paulo, Inst Biomed Sci, Human Genome Res Ctr, São Paulo, Brazil
dc.description.affiliation Univ São Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, São Paulo, Brazil
dc.description.affiliation Inst Israelita Ensino & Pesquisa Albert Einstein, Inst Cerebro, São Paulo, Brazil
dc.description.affiliation NIA, NIH, Bethesda, MD 20892 USA
dc.description.affiliation Helmholtz Zentrum Munchen, Inst Pathol, Neuherberg, Germany
dc.description.affiliationUnifesp Universidade Federal de São Paulo, São Paulo, Brazil
dc.identifier.doi 10.1530/ERC-13-0486
dc.description.source Web of Science
dc.identifier.wos WOS:000344787700021



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