RESUMEN
Endometrial carcinoma (EC) is the most frequent among infiltrating tumors of the female genital tract, with myometrial invasion representing an increase in the rate of recurrences and a decrease in survival. We have previously described ETV5 transcription factor associated with myometrial infiltration in human ECs. In this work, we further investigated ETV5 orchestrating downstream effects to confer the tumor the invasive capabilities needed to disseminate in the early stages of EC dissemination. Molecular profiling evidenced ETV5 having a direct role on epithelial-to-mesenchymal transition (EMT). In particular, ETV5 modulated Zeb1 expression and E-Cadherin repression leading to a complete reorganization of cell-cell and cell-substrate contacts. ETV5-promoted EMT resulted in the acquisition of migratory and invasive capabilities in endometrial cell lines. Furthermore, we identified the lipoma-preferred partner protein as a regulatory partner of ETV5, acting as a sensor for extracellular signals promoting tumor invasion. All together, we propose ETV5-transcriptional regulation of the EMT process through a crosstalk with the tumor surrounding microenvironment, as a principal event initiating EC invasion.
Asunto(s)
Proteínas de Unión al ADN/metabolismo , Neoplasias Endometriales/metabolismo , Transición Epitelial-Mesenquimal , Proteínas con Dominio LIM/metabolismo , Transducción de Señal , Factores de Transcripción/metabolismo , Cadherinas/metabolismo , Adhesión Celular/genética , Línea Celular Tumoral , Movimiento Celular/genética , Núcleo Celular/metabolismo , Proteínas de Unión al ADN/genética , Neoplasias Endometriales/genética , Transición Epitelial-Mesenquimal/genética , Femenino , Regulación Neoplásica de la Expresión Génica , Proteínas de Homeodominio/genética , Humanos , Regiones Promotoras Genéticas , Transporte de Proteínas , Factores de Transcripción/genética , Transcripción Genética , Homeobox 1 de Unión a la E-Box con Dedos de ZincRESUMEN
AIM: To compare the shaping ability of two rotary instruments in simulated curved canals: stainless steel ENDOflash Files (KaVo, Biberach, Germany) and the recently introduced nickel-titanium HERO Shaper instruments (Micro-Mega, Besançon, France). METHODOLOGY: Simulated root canals with 35 degree curves in resin blocks were prepared to size 30, .04 taper (HERO Shaper) using a crowndown technique or size 30, .02 taper (ENDOflash) using a rotary motion and a rotation speed of 400 or 250 rpm respectively. In both groups, irrigation was performed with 1 mL distilled water after each instrument size and Glyde (Dentsply Maillefer, Ballaigues, Switzerland) were used. Canals (n = 17 per group) were scanned before, during and after preparation. The assessment of preparation shape was carried out with a computer image analysis program. Material removal was measured at seven points beginning 1 mm from the end-point of the canal. Statistical analysis was performed using Wilcoxon's test and Fisher's exact test (P < 0.05). RESULTS: No instrument fractures, apical blockage or loss of working length (WL) occurred. More zips (10 vs. 4) and more strippings (17 vs. 0) were created with ENDOflash compared with the HERO Shaper. There were significant differences in terms of the amount of resin removed on the inner wall of the curvature obtained with the two instruments (P < 0.0001). On average, HERO Shaper instruments removed material more evenly on the outer and inner wall of the curvature. Considering the different points of measurement, there were significant differences between the two systems both on the inner and outer walls at WL-1, 2, 5 and 6 mm (P < 0.05). The HERO Shaper had a more centred enlargement compared with the ENDOflash. CONCLUSIONS: Stainless steel rotary ENDOflash instruments did not perform as well as HERO Shaper instruments and created an increased risk of root canal transportation. Nickel-titanium rotary HERO Shaper instruments maintained the original curvature significantly better.