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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

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

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Autor(es):
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Sekiya, Tomoko [1] ; Bronstein, Marcello D. [2] ; Benfini, Katiuscia ; Longuini, Viviane C. [1] ; Jallad, Raquel S. [2] ; Machado, Marcio C. [2] ; Goncalves, Tatiana D. ; Osaki, Luciana H. [3] ; Higashi, Leonardo [4] ; Viana-, Jr., Jose [5, 6] ; Kater, Claudio ; Lee, Misu ; Molatore, Sara [7] ; Francisco, Guilherme [8] ; Chammas, Roger [8] ; Naslavsky, Michel S. [9] ; Schlesinger, David [9, 10] ; Gama, Patricia [3] ; Duarte, Yeda A. O. [11] ; Lebrao, Maria Lucia [12] ; Zatz, Mayana ; Meirelles, Osorio [13] ; Liberman, Bernardo [4] ; Fragoso, Maria Candida B. V. [14] ; Toledo, Sergio P. A. [1] ; Pellegata, Natalia S. [7] ; Toledo, Rodrigo A. [1]
Número total de Autores: 27
Afiliação do(s) autor(es):
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[1] Univ Sao Paulo, Hosp Clin, Sch Med, Endocrine Genet Unit LIM 25, Sao Paulo - Brazil
[2] Univ Sao Paulo, Hosp Clin, Sch Med, Neuroendocrinol Unit, Sao Paulo - Brazil
[3] Univ Sao Paulo, Inst Biomed Sci, Dept Cell & Dev Biol, Sao Paulo - Brazil
[4] Brigadeiro Hosp, Sao Paulo - Brazil
[5] Univ Fed Sao Paulo, Sao Paulo - Brazil
[6] Santa Casa Hosp, Div Endocrinol, Sao Paulo - Brazil
[7] Helmholtz Zentrum Munchen, Inst Pathol, Neuherberg - Germany
[8] Univ Sao Paulo, Hosp Clin, Sch Med, Expt Oncol Lab LIM 24, Sao Paulo - Brazil
[9] Univ Sao Paulo, Inst Biomed Sci, Human Genome Res Ctr, Sao Paulo - Brazil
[10] Inst Israelita Ensino & Pesquisa Albert Einstein, Inst Cerebro, Sao Paulo - Brazil
[11] Univ Sao Paulo, Sch Nursing, Sao Paulo - Brazil
[12] Univ Sao Paulo, Sch Publ Hlth, Sao Paulo - Brazil
[13] NIA, NIH, Bethesda, MD 20892 - USA
[14] Univ Sao Paulo, Hosp Clin, Sch Med, Adrenal Unit LIM 42, Sao Paulo - Brazil
Número total de Afiliações: 14
Tipo de documento: Artigo Científico
Fonte: Endocrine-Related Cancer; v. 21, n. 3, p. 395-404, JUN 2014.
Citações Web of Science: 9
Resumo

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. (AU)

Processo FAPESP: 09/15386-6 - Análise dos genes CDKN1A, CDKN1B, CDKN2B e CDKN2C, nas Neoplasias Endócrinas Múltiplas tipo 1 e 2
Beneficiário:Rodrigo de Almeida Toledo
Linha de fomento: Bolsas no Brasil - Pós-Doutorado
Processo FAPESP: 13/01476-9 - Rastreamento de variantes de significado desconhecido (VUS) no proto-oncogene RET em pacientes com neoplasia endócrina múltipla tipo 2 e indivíduos saudáveis da população brasileira
Beneficiário:Sergio Pereira de Almeida Toledo
Linha de fomento: Auxílio à Pesquisa - Regular
Processo FAPESP: 09/11942-1 - Análise do gene CDKN1B/p27kip1 em pacientes com Neoplasia Endócrina Múltipla Tipo 2
Beneficiário:Tomoko Sekiya
Linha de fomento: Bolsas no Brasil - Doutorado Direto