RESUMEN
Zinc finger E-box-binding protein 2 (ZEB2) is known to help mediate the epithelial-to-mesenchymal transition, and thereby it facilitates cancer metastasis. This study was initiated to explore whether ZEB2 expression differs in prostate cancer (PCa, n=7) and benign prostatic hyperplasia (BPH, n=7) tissues. In PCa tissues, the levels of both immunoreactive ZEB2 and androgen receptor (AR) were found to be significantly higher (P<0.05) when compared with BPH tissues. Co-regulation of AR and ZEB2 prompted us to investigate the role of androgenic stimuli in ZEB2 expression. ZEB2 expression was found to be significantly (P<0.05) upregulated after androgen stimulation and downregulated following AR silencing in LNCaP cells, an androgen-dependent PCa cell line. This finding suggested AR as a positive regulator of ZEB2 expression in androgen-dependent cells. Paradoxically, androgen-independent (AI) cell lines PC3 and DU145, known to possess low AR levels, showed significantly (P<0.05) higher expression of ZEB2 compared with LNCaP cells. Furthermore, forced expression of AR in PC3 (PC3-AR) and DU145 (DU-AR) cells led to reductions in ZEB2 expression, invasiveness, and migration. These cells also exhibited an increase in the levels of E-cadherin (a transcriptional target of ZEB2). Co-transfection of AR and ZEB2 cDNA constructs prevented the decline in invasiveness and migration to a significant extent. Additionally, ZEB2 downregulation was associated with an increase in miR200a/miR200b levels in PC3-AR cells and with a decrease in miR200a/miR200b levels in AR-silenced LNCaP cells. Thus, AR acts as a positive regulator of ZEB2 expression in androgen-dependent cells and as a negative regulator in AI PCa cells.
Asunto(s)
Transición Epitelial-Mesenquimal , Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/metabolismo , MicroARNs/genética , Neoplasias de la Próstata/metabolismo , Neoplasias de la Próstata/patología , Receptores Androgénicos/metabolismo , Proteínas Represoras/metabolismo , Andrógenos/farmacología , Apoptosis/efectos de los fármacos , Western Blotting , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Dihidrotestosterona/farmacología , Técnica del Anticuerpo Fluorescente , Proteínas de Homeodominio/genética , Humanos , Técnicas para Inmunoenzimas , Masculino , Neoplasias Hormono-Dependientes/tratamiento farmacológico , Neoplasias Hormono-Dependientes/genética , Neoplasias Hormono-Dependientes/metabolismo , Neoplasias Hormono-Dependientes/patología , Hiperplasia Prostática/tratamiento farmacológico , Hiperplasia Prostática/genética , Hiperplasia Prostática/metabolismo , Hiperplasia Prostática/patología , Neoplasias de la Próstata/tratamiento farmacológico , Neoplasias de la Próstata/genética , ARN Mensajero/genética , ARN Interferente Pequeño/genética , Reacción en Cadena en Tiempo Real de la Polimerasa , Receptores Androgénicos/química , Receptores Androgénicos/genética , Proteínas Represoras/genética , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa , Células Tumorales Cultivadas , Cicatrización de Heridas , Caja Homeótica 2 de Unión a E-Box con Dedos de ZincRESUMEN
A unique case is described of an ingested fish bone migrating into the common hepatic duct, without perforation. Most foreign bodies are known to pass through the gastrointestinal tract uneventfully. Sharper objects such as fish bones have been known to cause perforation. This is more common, in countries where fish consumption is considerably higher, such as, south east Asia. However, even in these regions there have been no reports of such a proximal migration.