RESUMO
BACKGROUND: Here we evaluate auto-antibody response against two potential antigenic determinants of genes highly expressed in low Gleason Score prostate cancer (PC) tumor samples, namely FLJ23438 and VAMP3. METHODS: RT-PCR assays were used to analyze mRNA expression profiles of FLJ23438 and VAMP3 transcripts. The auto-antibody response against FLJ23438 and VAMP3 recombinant proteins was tested by immunoblot assays using PC, benign prostate hyperplasia (BPH), healthy donors (HD), and other human cancers plasma samples. RESULTS: Our data showed that 37% (10/27) and 7.4% (2/27) of PC plasma samples presented auto-antibodies against FLJ23438 and VAMP3, respectively. Only 8.3% (1/12) of BPH plasma samples were reactive for both auto-antibodies, while none (0/12) of HD plasma samples tested were reactive. CONCLUSIONS: The prevalence of 37% of positive PC plasma samples for anti-FLJ23438 antibodies suggests that humoral immune response against this antigenic determinant could be a potential serum marker for this cancer.
Assuntos
Adenocarcinoma/imunologia , Autoanticorpos/sangue , Biomarcadores Tumorais/imunologia , Neoplasias da Próstata/imunologia , Proteína 3 Associada à Membrana da Vesícula/imunologia , Adenocarcinoma/epidemiologia , Adenocarcinoma/fisiopatologia , Idoso , Antígenos/genética , Antígenos/imunologia , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Neoplasias da Mama , Carcinoma de Células Escamosas , Linhagem Celular Tumoral , Neoplasias Colorretais , Neoplasias Esofágicas , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares , Masculino , Pessoa de Meia-Idade , Fases de Leitura Aberta/genética , Hiperplasia Prostática/epidemiologia , Hiperplasia Prostática/imunologia , Hiperplasia Prostática/fisiopatologia , Neoplasias da Próstata/epidemiologia , Neoplasias da Próstata/fisiopatologia , RNA Mensageiro/genética , RNA Nuclear Pequeno/genética , RNA Nuclear Pequeno/imunologia , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Estudos Soroepidemiológicos , Proteína 3 Associada à Membrana da Vesícula/genéticaRESUMO
Mutations in different exons of ret proto-oncogene are responsible for the development of medullary thyroid carcinoma (MTC). The mutations can occur as sporadic or as part of multiple endocrine neoplasia (MEN) type 2 hereditary syndromes. Here we report the first focused study of sporadic MTC in Brazilian patients regarding clinical and molecular analysis of ret proto-oncogene. Our study seeks to estimate the risk of hereditary MTC cases among apparently sporadic cases in a Brazilian population and describe ret genetic variants in their germinative lineage. Germinative sequence variants were screened by DNA sequencing and denaturing gradient gel electrophoresis (DGGE) analysis of exons 10, 11, 13, 14, 15, and 16 of 24 Brazilian patients with apparently sporadic MTC. We identified 1 inherited case of 24 (4%) patients with apparently sporadic MTC. Polymorphisms for the ret proto-oncogene coding region were identified in codon 769 of exon 13 (LeuCTT--> LeuCTG) at a frequency of 13% (3/24) and in codon 904 of exon 15 (SerTCC--> SerTCG) at a frequency of 16.6% (4/24). The observed frequency (4%) of inherited disease among apparent sporadic MTC strengthens routine application of ret proto-oncogene germinative DNA screening in all cases of apparently sporadic MTC ascertained at Brazilian cancer hospitals.
Assuntos
Carcinoma Medular/genética , Proteínas Proto-Oncogênicas c-ret/genética , Neoplasias da Glândula Tireoide/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil/epidemiologia , Carcinoma Medular/epidemiologia , Carcinoma Medular/patologia , Códon/genética , DNA/biossíntese , DNA/genética , Éxons/genética , Feminino , Frequência do Gene , Variação Genética , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Polimorfismo Genético/genética , Proto-Oncogene Mas , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Neoplasias da Glândula Tireoide/epidemiologia , Neoplasias da Glândula Tireoide/patologiaRESUMO
We report here for the first time the structure and function of a promoter from a cestode. The ability of DNA fragments respectively encompassing the 935-bp and 524-bp regions upstream from the ATG codon from the EgactI and EgactII actin genes of Echinococcus granulosus to promote transcription was studied in the NIH3T3 mouse cell line. The results of transfection assays showed that both regions have strong promoter activity in these cells. The fragments were tested in both orientations and the 524-bp fragment of EgactII presented a bidirectional promoter activity. Deletion analysis of EgactI and EgactII promoters indicated the presence of regulatory regions containing putative silencer elements. These results indicate that both EgactI and EgactII promoters are functional and that the preliminary functional evaluation of E. granulosus and possibly of other cestode promoters can be performed in heterologous cell lines
