Breast Cancer Epigenetics: From DNA Methylation to microRNAs

Both appropriate DNA methylation and histone modifications play a crucial role in the maintenance of normal cell function and cellular identity. In cancerous cells these “epigenetic belts” become massively perturbed, leading to significant changes in expression profiles which confer advantage to the development of a malignant phenotype. DNA (cytosine-5)-methyltransferase 1 (Dnmt1), Dnmt3a and Dnmt3b are the enzymes responsible for setting up and maintaining DNA methylation patterns in eukaryotic cells. Intriguingly, DNMTs were found to be overexpressed in cancerous cells, which is believed to partly explain the hypermethylation phenomenon commonly observed in tumors. However, several lines of evidence indicate that further layers of gene regulation are critical coordinators of DNMT expression, catalytic activity and target specificity. Splice variants of DNMT transcripts have been detected which seem to modulate methyltransferase activity. Also, the DNMT mRNA 3′UTR as well as the coding sequence harbors multiple binding sites for trans-acting factors guiding post-transcriptional regulation and transcript stabilization. Moreover, microRNAs targeting DNMT transcripts have recently been discovered in normal cells, yet expression of these microRNAs was found to be diminished in breast cancer tissues. In this review we summarize the current knowledge on mechanisms which potentially lead to the establishment of a DNA hypermethylome in cancer cells

Abordagem sistêmica do gerenciamento pelas diretrizes: conceituação e aplicação A systematic approach to policy deployment: concept and application

Este artigo apresenta um modelo teórico do Gerenciamento pelas Diretrizes (GD), organizando suas principais características sob uma ótica conceitual, explorando os seus aspectos orgânicos. Inicialmente, é estabelecido o seu processo característico para, em seguida, serem definidos quatro elementos que o complementam: (1) sistema de priorização; (2) dispositivos estruturais; (3) dispositivos conciliadores; e (4) sistema de informação. A partir desta referência e por meio da pesquisa-ação é articulada sua implementação numa empresa de serviços que atua como distribuidor de cerveja, atendendo uma grande região geográfica. Desta intervenção, surgem novas características que contribuem para o aprimoramento da proposta.<br>This article presents the theoretical model of policy deployment, exploring and organizing its organic features. At first, the featuring process is established, afterwards four complementary elements are defined: the priority system, the structural devices, the conciliatory devices and the information system. The test is done by research method, "research by intervention in one reality". The intervention was promoted in a beer retailer that operates covering a wide geographic area. New findings were gotten therefore leading condition to improve the model proposed