RESUMEN
Until recently, works on the microscopic anatomy of the human intestinal villus had been hampered by lack of in vivo observations, and were based on early corrosion cast techniques before the advent of scanning electron microscopy to correctly identify the nature of the vessels seen. On review, a large number of human anatomy and histology texts carry a possibly erroneous message, as is the same with the earlier works, that there are arterioles and venules in the core of these villi. Based on recently available high resolution in vivo observations by endoscopy, our work by transmission electron microscopy and light microscopy techniques on cross sections of the villi shows only capillary type channels, and such is also true of those anatomy and histology textbooks that have photomicrographs of cross sections of the villi (despite their possible errors). An analytical discussion in further support of our findings is made, based on established anatomical and physiological principles
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Asunto(s)
Humanos , Intestinos/ultraestructura , Vasos Sanguíneos/ultraestructura , Microcirculación , Microvellosidades/ultraestructura , Microscopía Electrónica de Transmisión/métodosRESUMEN
We reported previously that the loss of expression of estrogen receptor (ER)-beta during the development of prostate cancer (PCa) is associated with methylation of a CpG island located in the 5'-flanking sequence of the 0N promoter. Three methylation hotspots, referred to as centers 1, 2 and 3, were identified in the CpG island. In this study, we demonstrated that a 581-bp region with these three centers within it is sufficient for the promoter activity in PCa cells. Deletion analyses indicated that center 1 (16 bp), with a putative activator protein-2 (AP-2) binding site, is essential for gene transactivation. Chromatin immunoprecipitation assays showed that AP-2alpha occupies a short sequence containing center 1. Forced expression of AP-2alpha or -2gamma, but not -2beta, increased activity of the ERbeta 0N promoter and the accumulation of mRNA. Conversely, siRNA-mediated AP-2alpha and -2gamma knockdown reduced levels of ERbeta transcript and promoter activity. Quantitative reverse transcription-PCR showed that AP-2alpha and -2gamma are the predominant transcripts expressed in PCa cells, and levels of ERbeta transcript correlate with levels of these AP-2 transcripts among different PCa cell lines. These results provide the first evidence that ERbeta is an AP-2-regulated gene. They also support the hypothesis that certain cis-acting elements are methylation hotspots susceptible to epigenetic modifications during cancer progression.
Asunto(s)
Metilación de ADN , Receptor beta de Estrógeno/genética , Regulación Neoplásica de la Expresión Génica , Regiones Promotoras Genéticas , Neoplasias de la Próstata/genética , Factor de Transcripción AP-2/metabolismo , Inmunoprecipitación de Cromatina , Islas de CpG , Receptor beta de Estrógeno/metabolismo , Humanos , Masculino , Neoplasias de la Próstata/metabolismo , ARN Mensajero/genética , ARN Mensajero/metabolismo , ARN Interferente Pequeño/farmacología , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Eliminación de Secuencia , Factor de Transcripción AP-2/antagonistas & inhibidores , Factor de Transcripción AP-2/genética , Transcripción Genética , Células Tumorales CultivadasRESUMEN
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