RESUMEN
Reck (REversion-inducing Cysteine-rich protein with Kazal motifs) tumor suppressor gene encodes a multifunctional glycoprotein which inhibits the activity of several matrix metalloproteinases (MMPs), and has the ability to modulate the Notch and canonical Wnt pathways. Reck-deficient neuro-progenitor cells undergo precocious differentiation; however, modulation of Reck expression during progression of the neuronal differentiation process is yet to be characterized. In the present study, we demonstrate that Reck expression levels are increased during in vitro neuronal differentiation of PC12 pheochromocytoma cells and P19 murine teratocarcinoma cells and characterize mouse Reck promoter activity during this process. Increased Reck promoter activity was found upon induction of differentiation in PC12 cells, in accordance with its increased mRNA expression levels in mouse in vitro models. Interestingly, Reck overexpression, prior to the beginning of the differentiation protocol, led to diminished efficiency of the neuronal differentiation process. Taken together, our findings suggest that increased Reck expression at early stages of differentiation diminishes the number of neuron-like cells, which are positive for the beta-3 tubulin marker. Our data highlight the importance of Reck expression evaluation to optimize in vitro neuronal differentiation protocols.
Asunto(s)
Proteínas Ligadas a GPI/metabolismo , Genes Supresores de Tumor , Neurogénesis/genética , Teratocarcinoma/metabolismo , Animales , Sitios de Unión , Citometría de Flujo , Proteínas Ligadas a GPI/genética , Regulación Neoplásica de la Expresión Génica/genética , Ratones , Células PC12 , Regiones Promotoras Genéticas , Ratas , Reacción en Cadena en Tiempo Real de la Polimerasa , Teratocarcinoma/genética , Tubulina (Proteína)/metabolismo , Regulación hacia ArribaRESUMEN
BACKGROUND: Genital wart (GW) incidence is high among men. The percentage and rate at which subsequent GW events occur are understudied. The purpose of this study was to describe the rate of subsequent GWs, associated human papillomavirus (HPV) types, and time to subsequent GW event among unvaccinated men. METHODS: The study was nested within a multinational prospective HPV natural history study of men aged 18-70 years in the United States, Mexico, and Brazil, examined every 6 months for a median follow-up of 50.4 months. Subsequent GW events were defined as GWs detected after ≥16 weeks of the prior event. RESULTS: Forty-four percent of men experienced ≥1 GW following the initial episode. Men with ≥2 subsequent events were at highest risk of continued GW experiences, with as high as 10 postinitial GW events. The incidence rate of each subsequent GW increased with increasing events (incidence of first subsequent event was 13.1 vs 36.6/1000 person-months for the fourth event). The proportion of GWs among HPV-6 and/or -11-positive patients remained constant across events. Approximately 63%-69% were positive for ≥1 of the 9-valent HPV vaccine types. CONCLUSIONS: These data highlight the high burden of GWs among men across the lifespan and the need for vaccination to prevent multiple GW episodes.