RESUMEN
Family with sequence similarity 20-member C (FAM20C) is a kinase specific to most of the secreted phosphoproteome. FAM20C has been identified as the causative gene of Raine syndrome, initially characterized by lethal osteosclerosis bone dysplasia. However, since the identification of the cases of nonlethal Raine syndrome characterized by hypophosphatemia rickets, the previous definition of Raine syndrome has become debatable and raised a question about the role of mutations of FAM20C in controversial skeletal manifestation in the two forms of the disease. In this study, we aimed to investigate the influence of FAM20C mutations on skeletogenesis. We developed transgenic mice expressing Fam20c mutations mimicking those associated with human lethal and nonlethal Raine syndrome. The results revealed that transgenic mice expressing the mutant Fam20c found in the lethal (KO;G374R) and nonlethal (KO;D446N) Raine syndrome exhibited osteomalacia without osteosclerotic features. Additionally, both mutants significantly increased the expression of the Fgf23, indicating that Fam20c deficiency in skeletal compartments causes hypophosphatemia rickets. Furthermore, as FAM20C kinase activity catalyzes the phosphorylation of secreted proteomes other than those in the skeletal system, global FAM20C deficiency may trigger alterations in other systems resulting in osteosclerosis secondary to hypophosphatemia rickets. Together, the findings of this study suggest that FAM20C deficiency primarily causes hypophosphatemia rickets or osteomalacia; however, the heterogeneous skeletal manifestation in Raine syndrome was not determined solely by specific mutations of FAM20C. The findings also implicated that rickets or osteomalacia caused by FAM20C deficiency would deteriorate into osteosclerosis by the defects from other systems or environmental impacts.
Asunto(s)
Hipofosfatemia , Osteomalacia , Osteosclerosis , Raquitismo , Ratones , Animales , Humanos , Osteomalacia/complicaciones , Osteomalacia/genética , Osteosclerosis/genética , Osteosclerosis/complicaciones , Mutación/genética , Raquitismo/complicaciones , Ratones Transgénicos , Hipofosfatemia/genética , Hipofosfatemia/complicaciones , Proteínas de la Matriz Extracelular/genética , Proteínas de la Matriz Extracelular/metabolismo , Proteínas de Unión al Calcio/genéticaRESUMEN
Genistein, a plant isoflavone, is reported to have therapeutic potentials in multiple cancers, However, the molecular mechanism underlying promoting cell apoptosis in laryngeal cancer remains unclear. In this study, we report that miR-1469 was induced by genistein in laryngeal cancer. Elevated miR-1469 promoted cell apoptosis and inhibited Mcl1 expression. In addition, we also observed that tumor suppressor p53 was increased under genistein treatment. Elevation of p53 promoted miR-1469 expression, leading to miR-1469 increase and Mcl1 decrease. Therefore, our findings suggest that genistein can suppress laryngeal cancer cell survival through p53 -miR-1469-Mcl1pathway.
Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Genisteína/farmacología , Neoplasias Laríngeas/tratamiento farmacológico , MicroARNs/fisiología , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Laríngeas/genética , Neoplasias Laríngeas/metabolismo , Neoplasias Laríngeas/patología , MicroARNs/genética , Proteína 1 de la Secuencia de Leucemia de Células Mieloides/genética , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Proteína p53 Supresora de Tumor/genéticaRESUMEN
OBJECTIVES: We explored a potential association between nasal polyps (NPs) and polymorphism at loci for human leukocyte antigen (HLA) DR and HLA-DQ. METHODS: Polymorphism at loci HLA-DR and HLA-DQ were examined in 30 patients with NPs and in 81 healthy subjects by use of the polymerase chain reaction-sequence specific primer method. RESULTS: HLA-DR16, HLA-DQ8, and HLA-DQ9 were found to be significantly associated with NPs. HLA-DR16, HLA-DQ8, and HLA-DQ9 specificities were found at higher frequencies in patients with NPs than in control subjects (5% versus 0.62%, RR = 8.9, p = .03; 10% versus 2.47%, RR = 4.81, p = .01; and 20% versus 6.18%, RR = 4.73%, p = .001; respectively). In contrast, HLA-DQ7 was found at lower frequencies in patients with NPs than in controls (10% versus 20.37%, RR = 0.36, p = .04). CONCLUSIONS: We conclude that HLA-DR16, HLA-DQ8, and HLA-DQ9 represent potential susceptibility determinants and that HLA-DQ7 might confer resistance in nasal polyps.
Asunto(s)
Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Pólipos Nasales/genética , Polimorfismo Genético , Adulto , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Humanos , Masculino , Pólipos Nasales/inmunologíaRESUMEN
A 55 year old man complained of a painless mass at the left maxillofacial region. The mass had continuously grown over 10 years. Upon physical examination a cystic mass with size of 5 cm in length with bulging smooth surface was seen on the left maxillofacial region. Computed tomography (CT) scan showed a giant cyst with bone destruction and invasion in the left maxilla, maxillary sinus and nasal cavity. Needle aspiration of the mass yielded 80 milliliter of brown fluid. The excisional biopsy was made which revealed ghost cells and dysplastic dentin that were features of dentinogenic ghost cell tumor. Finally, a dentinogenic ghost cell was diagnosed.