RESUMO
BACKGROUND: A member of the genes encoding WD-repeat proteins, the WDR3 gene, maps in the 1p12 region. This region was shown to be associated with thyroid cancer susceptibility in a previous work. In this study we aim to evaluate the contribution of WDR3 to thyroid cancer risk. METHODS: A case-control association study was performed in a total of 402 patients and 479 control subjects from a Spanish population. In the initial phase of the study, 10 single-nucleotide polymorphisms covering the WDR3 region were genotyped in a small group (157 patients and 118 control subjects); next, three of the initial single-nucleotide polymorphisms were further genotyped in the overall population. In addition, WDR3 expression was investigated in 10 thyroid cancer cell lines by RT-PCR and Western blot. RESULTS: Haplotype analysis revealed that combination of certain WDR3 variants, such as haplotype CAT, increases the risk of thyroid cancer (odds ratio = 1.85, 95% confidence interval = 0.97-3.55, p = 0.063). Further, both messenger RNA transcription and protein expression of WDR3 were altered in human thyroid cancer cells. CONCLUSION: These results indicate for the first time that WDR3 is a risk factor to thyroid cancer, suggesting its implication in the etiology of thyroid cancer.
Assuntos
Predisposição Genética para Doença , Haplótipos , Proteínas Nucleares/genética , Neoplasias da Glândula Tireoide/genética , Adenocarcinoma Folicular/epidemiologia , Adenocarcinoma Folicular/genética , Adulto , Carcinoma Papilar/epidemiologia , Carcinoma Papilar/genética , Estudos de Casos e Controles , Linhagem Celular Tumoral , Feminino , Regulação Neoplásica da Expressão Gênica , Frequência do Gene , Estudos de Associação Genética , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Proteínas Nucleares/metabolismo , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/metabolismo , Fatores de Risco , Espanha/epidemiologia , Neoplasias da Glândula Tireoide/epidemiologia , Regulação para Cima , Adulto JovemRESUMO
Prostate proliferation is dependent of androgens and many peptide hormones. Recent reports suggest that SSTR2 and SHP-1 were two fundamental components on antiproliferative effect of somatostatin. Many studies on SHP-1 revealed that the expression of this protein was diminished or abolished in several of the cancer cell lines and tissues examined. However, it is necessary to confront the cell lines data with real situation in cancer cases. Our studies have shown that epithelial expressions of both proteins, SHP-1 and SSTR2, in normal and benign hyperplasia are localized in the luminal side of duct and acinar cells. Also, SSTR2 is expressed in stromal cells. In malignant prostate tissue, SHP-1 was diminished in 28/45 cases or absent in 12/45 cases, whereas SSTR2 epithelial was diminished in 38/45 cases or lost in only 2/45 cases. The intensity of immunostained was highly negative correlated with Gleason grade for two proteins.
