RESUMO
Mutations in the BRCA1-interacting DEAH helicase Brip1 confer an increased risk of breast cancer. In the present study we aimed to unravel the transcriptional control of Brip1 and to determine its expression levels in a set of 101 primary invasive breast carcinomas. Transcription of Brip1 was found to be cell growth-related and controlled by the E2F/retinoblastoma (Rb) pathway through a conserved E2F-responsive site. Repression of Brip1 expression by the cell growth-inhibiting compound 1alpha,25-dihydroxyvitamin D3 depended on this same E2F-responsive site. In spite of its role as a tumor suppressor, both quantitative reverse transcriptase-PCR analyses and immunohistochemical stainings showed significantly elevated Brip1 expression levels in grade 3 tumors as compared to grade 1 or 2 carcinomas. Furthermore, increased Brip1 transcript levels were found in tumors with an estrogen receptor-negative, progesterone receptor-negative or HER-2-positive status. In conclusion, these data show that Brip1 is a genuine target gene for the E2F/Rb pathway and that elevated expression levels of Brip1 are detected in primary invasive breast carcinomas with unfavorable characteristics.
Assuntos
Neoplasias da Mama/genética , Carcinoma/genética , Proteínas de Ligação a DNA/genética , Fatores de Transcrição E2F/fisiologia , Regulação Neoplásica da Expressão Gênica , RNA Helicases/genética , Animais , Sequência de Bases , Fatores de Transcrição de Zíper de Leucina Básica/genética , Sítios de Ligação , Neoplasias da Mama/patologia , Carcinoma/patologia , Sequência Conservada , Fatores de Transcrição E2F/metabolismo , Proteínas de Grupos de Complementação da Anemia de Fanconi/genética , Feminino , Humanos , Camundongos , Dados de Sequência Molecular , Invasividade Neoplásica , Homologia de Sequência do Ácido Nucleico , Transcrição Gênica , Células Tumorais CultivadasAssuntos
Proteínas de Bactérias/genética , Células Epiteliais/microbiologia , Análise em Microsséries/métodos , Salmonella typhimurium/genética , Salmonella typhimurium/fisiologia , Transativadores/genética , Aderência Bacteriana , Regulação Bacteriana da Expressão Gênica , Genes Reguladores , Genoma Bacteriano , Análise Serial de Proteínas , Salmonella typhimurium/patogenicidade , Transcrição GênicaRESUMO
We investigated whether prognostic information is reflected in the expression patterns of ovarian carcinoma samples. RNA obtained from seven FIGO stage I without recurrence, seven platin-sensitive advanced-stage (III or IV), and six platin-resistant advanced-stage ovarian tumors was hybridized on a complementary DNA microarray with 21,372 spotted clones. The results revealed that a considerable number of genes exhibit nonaccidental differential expression between the different tumor classes. Principal component analysis reflected the differences between the three tumor classes and their order of transition. Using a leave-one-out approach together with least squares support vector machines, we obtained an estimated classification test accuracy of 100% for the distinction between stage I and advanced-stage disease and 76.92% for the distinction between platin-resistant versus platin-sensitive disease in FIGO stage III/IV. These results indicate that gene expression patterns could be useful in clinical management of ovarian cancer.
Assuntos
Adenocarcinoma/genética , Adenocarcinoma/patologia , Neoplasias Ovarianas/genética , Neoplasias Ovarianas/patologia , Adenocarcinoma/tratamento farmacológico , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos/uso terapêutico , Resistencia a Medicamentos Antineoplásicos , Feminino , Perfilação da Expressão Gênica , Humanos , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Ovarianas/tratamento farmacológico , Compostos de Platina/uso terapêutico , Valor Preditivo dos TestesRESUMO
Quorum sensing (QS) in Gram-negative bacteria is generally assumed to be mediated by N-acyl-homoserine lactone molecules while Gram-positive bacteria make use of signaling peptides. We analyzed the occurrence in Gram-negative bacteria of peptides and transporters that are involved in quorum sensing in Gram-positive bacteria. Many class II bacteriocins and inducing factors produced by lactic acid bacteria (LAB) and competence stimulating peptides (CSPs) synthesized by streptococci are processed by their cognate ABC-transporters during their secretion. During transport, a conserved leader sequence, termed the double-glycine motif (GG-motif), is cleaved off by the N-terminal domain of the transporter, which belongs to the Peptidase C39 protein family. Several peptides containing a GG-motif were recently described in Gram-negative bacteria (Trends Microbiol 2001;9:164-8). To screen for additional putative GG-motif containing peptides, an in silico strategy based on MEME, HMMER2.2 and Wise2 was designed. Using a curated training set, a motif model of the leader peptide was built and used to screen over 120 fully sequenced bacterial genomes. The screening methodology was applied at the nucleotide level as probably many small peptide genes have not been annotated and may be absent from the non-redundant databases. It was found that 33% of the screened genomes of Gram-negative bacteria contained one or more transporters carrying a Peptidase C39 domain, compared to 44% of the genomes of Gram-positive bacteria. The transporters can be subdivided into four classes on the basis of their domain organization. Genes coding for putative peptides containing 23-142 amino acids and a GG-motif were found in close association with genes coding for Peptidase C39 domain containing proteins. These peptides show structural similarity to bacteriocins and peptide pheromones of Gram-positive bacteria. The possibility of signal transduction based on peptide signaling in Gram-negative bacteria is discussed.