RESUMEN
Midkine (MK), a retinoic acid responsible protein, is regulated during development and may play an important role in tumorigenesis. A search for genetic variations of the MK gene, located on chromosome 11q11.2 in humans, has not yet been conducted in cancers. To examine the entire coding region, as well as 4 regions of the promoter covering all functional motifs, 8 sets of intron-based and promoter region primers were designed. Using these primers, polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) analysis of genomic DNA samples from 60 sporadic colorectal and 37 sporadic gastric cancer patients was carried out. This analysis, followed by DNA sequencing, revealed a heterozygous g/t polymorphism at the 62nd base on intron 3 in five colorectal tumors (8.3%) and one gastric tumor (2.7%). In the promoter region, a heterozygous CTT deletion, creating a (CTTTT)2 repeat, in one colorectal cancer sample (1.67%) and a heterozygous 2-bp deletion in the G7 tract in another colorectal cancer patient were detected. A/G and A/A alleles were also detected at nt. -1741 in 36 (97.3%) and one (2.7%) gastric cancer samples, respectively. The A/G alleles were observed in all colorectal cancer patients (100%). All variations observed in the promoter region showed polymorphism. These results suggest that in sporadic colorectal and gastric cancers some gene alterations are present in the MK promoter region, but alterations in the coding region are rare.
Asunto(s)
Proteínas Portadoras/genética , Neoplasias Colorrectales/genética , Citocinas , Variación Genética , Neoplasias Gástricas/genética , Alelos , Cromosomas Humanos Par 11/genética , Cartilla de ADN/química , ADN de Neoplasias/análisis , Exones , Femenino , Eliminación de Gen , Frecuencia de los Genes , Humanos , Masculino , Midkina , Reacción en Cadena de la Polimerasa , Polimorfismo Genético/genética , Polimorfismo Conformacional Retorcido-Simple , Análisis de Secuencia de ADNRESUMEN
To clarify whether the changes of free radicals and its scavengers are induced by thyroid disorders, we measured levels of free radical scavengers and checked O2 radical generating systems in the human thyroid gland. Thyroid specimens from patients with Graves' disease, follicular adenoma, and papillary and follicular carcinomas contained significantly higher concentrations of xanthine oxidase (XOD) and gluthathione peroxidase (GSH-PX), compared to those in the normal thyroid tissue. Catalase concentration was significantly lower in thyroid specimens from patients with Graves' disease and significantly lower in thyroid specimens from patients with follicular adenoma, compared to those in the normal thyroid tissue. Cu/Zn superoxide dismutase (Cu/Zn SOD) concentration was significantly lower in the specimens from follicular adenoma and papillary carcinoma and Mn SOD concentration was significantly higher in the specimens from papillary carcinoma than those in the normal thyroid tissue. The lipid peroxide concentration, expressed as malondialdehyde (MDA) concentration, was significantly higher in the specimens from papillary carcinoma than those in the normal thyroid tissue. These findings suggest that the levels of free radicals are increased and are scavenged and catalyzed in the thyroid of Graves' disease, whereas free radicals and lipid peroxide are not completely scavenged in papillary carcinoma tissues, suggesting that these substances affect some role in cell function of thyroid tumors.