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

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

Author Sekiya, Tomoko Google Scholar
Bronstein, Marcello D. Google Scholar
Benfini, Katiuscia Google Scholar
Longuini, Viviane C. Google Scholar
Jallad, Raquel S. Google Scholar
Machado, Marcio C. Google Scholar
Goncalves, Tatiana D. Google Scholar
Osaki, Luciana H. Google Scholar
Higashi, Leonardo Google Scholar
Viana-Junior, Jose Autor UNIFESP Google Scholar
Kater, Claudio Google Scholar
Lee, Misu Google Scholar
Molatore, Sara Google Scholar
Francisco, Guilherme Google Scholar
Chammas, Roger Google Scholar
Naslavsky, Michel S. Google Scholar
Schlesinger, David Google Scholar
Gama, Patricia Google Scholar
Duarte, Yeda A. O. Google Scholar
Lebrao, Maria Lucia Google Scholar
Zatz, Mayana Google Scholar
Meirelles, Osorio Google Scholar
Liberman, Bernardo Google Scholar
Fragoso, Maria Candida B. V. Google Scholar
Toledo, Sergio P. A. Google Scholar
Pellegata, Natalia S. Google Scholar
Toledo, Rodrigo A. Google Scholar
Institution Universidade de São Paulo (USP)
Santa Casa Hosp
Brigadeiro Hosp
Universidade Federal de São Paulo (UNIFESP)
Inst Israelita Ensino & Pesquisa Albert Einstein
NIA
Helmholtz Zentrum Munchen
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.
Keywords endocrine tumor
p27
corticotropinoma
pituitary tumor
Language English
Sponsor Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
Date 2014-06-01
Published in Endocrine-related Cancer. Bristol: Bioscientifica Ltd, v. 21, n. 3, p. 395-404, 2014.
ISSN 1351-0088 (Sherpa/Romeo, impact factor)
Publisher Bioscientifica Ltd
Extent 395-404
Origin http://dx.doi.org/10.1530/ERC-13-0486
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000344787700021
URI http://repositorio.unifesp.br/handle/11600/37807

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