RESUMO
Pancreatic ductal adenocarcinoma (PDAC) has an extremely poor prognosis. To improve diagnosis and treatment, key mechanisms of deregulated molecular functions have to be identified. Using microarray analysis, the expression patterns of 5600 human genes were assessed in PDAC by comparison with the normal pancreas and chronic pancreatitis (CP). The expression of 467 of 5600 genes was increased in PDAC in comparison to the normal pancreas, and the expression of 120 of these genes was not increased in CP. In addition, 341 of 5600 genes were expressed at decreased levels in PDAC tissues, of which 96 were decreased in comparison to both normal and CP tissues. Thus, a total of 808 of 5600 human genes were differentially expressed in pancreatic cancer. The identification of a large panel of altered genes in PDAC will stimulate additional studies that will lead to improved understanding of the molecular mechanisms underlying pancreatic malignant growth.
Assuntos
Adenocarcinoma/genética , Neoplasias Pancreáticas/genética , Adenocarcinoma/patologia , Adenocarcinoma/secundário , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Perfilação da Expressão Gênica , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Sequência com Séries de Oligonucleotídeos , Neoplasias Pancreáticas/patologia , Pancreatite/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Fator de Crescimento Transformador beta/genéticaRESUMO
The helix-turn-helix domain-containing family of transcriptional regulators is of ancient origin and has been incorporated into numerous disparate biological processes. As a consequence, the forces shaping its early evolution have been difficult to reconstruct. Herein, we analyze this large and diverse family with a combination of traditional phylogenetic techniques and newer sequence analysis tools to determine whether the helix-turn-helix family arose from a single common ancestor. Our analyses of the DNA-binding domain show that amino acid chemistry is conserved at many sites in the first helix and the turn. The high level of divergence combined with the short length of the domain hinders robust reconstruction of the entire phylogeny, but some level of deep node inference is possible. All analyses point to a predominantly monophyletic origin for the helix-turn-helix domain. The consequences of such an origin for a diverse group of proteins, and guidelines for the identification of future members of the HTH family are discussed.
Assuntos
Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/genética , Evolução Molecular , Sequências Hélice-Volta-Hélice , Fatores de Transcrição/química , Fatores de Transcrição/genética , Sequência de Aminoácidos , Sequência Conservada , Dados de Sequência Molecular , Filogenia , Estrutura Secundária de Proteína , Alinhamento de Sequência , Homologia de Sequência de AminoácidosRESUMO
The Myb family of proteins is a group of functionally diverse transcriptional activators found in both plants and animals that is characterized by a conserved DNA-binding domain of approximately 50 amino acids. Phylogenetic analyses of amino acid sequences of this family of proteins portray very disparate evolutionary histories in plants and animals. Animal Myb proteins have diverged from a common ancestor, while plants appear related only within the DNA-binding domain. Results imply a pattern of modular evolution of the Myb proteins centering on the possession of a helix-turn-helix motif. Based on this it is suggested that Myb proteins are a polyphyletic group related only by a "Myb-box" DNA-binding motif.
