| Full text | |
| Author(s): Show less - |
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]
Total Authors: 27
|
| Affiliation: Show less - | [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
Total Affiliations: 14
|
| Document type: | Journal article |
| Source: | Endocrine-Related Cancer; v. 21, n. 3, p. 395-404, JUN 2014. |
| Web of Science Citations: | 9 |
| 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. (AU) | |
| FAPESP's process: | 09/15386-6 - Analysis of the CDKN1A, CDKN1B, CDKN2B and CDKN2C genes in multiple endocrine neoplasias type 1 and 2. |
| Grantee: | Rodrigo de Almeida Toledo |
| Support Opportunities: | Scholarships in Brazil - Post-Doctoral |
| FAPESP's process: | 09/11942-1 - Analysis of CDKN1B/p27kip1 gene in patients with Multiple Endocrine Neoplasia Type 2 |
| Grantee: | Tomoko Sekiya |
| Support Opportunities: | Scholarships in Brazil - Doctorate (Direct) |
| FAPESP's process: | 13/01476-9 - Screening of variants of unkown significance (VUS) in the RET proto-oncogene in patients with multiple endocrine neoplasia type 2 and healthy individual controls |
| Grantee: | Sergio Pereira de Almeida Toledo |
| Support Opportunities: | Regular Research Grants |