RESUMEN
Apart from the regulation of calcium metabolism, 1, 25-dihydroxyvitamin D(3) plays an essential role in cell proliferation and differentiation in several tissues. The vitamin D receptor (VDR) gene shows polymorphisms in humans that appear to be clinically significant in some pathological conditions. In the present study, the BsmI polymorphism of the VDR gene was studied in 59 Caucasian patients with rectal cancer (mean follow-up: 48 months). The relationship between VDR genotypes and the expression of oncogenes as well as their influence on survival were also investigated. VDR polymorphism was examined in tumor and normal mucosa cells by PCR technique. The expression of erbB-2/HER-2, p53, ras and epidermal growth factor receptor (EGFR) was also detected by immunohistochemistry and protein blotting. The presence of the VDR B allele significantly correlated with the overexpression of the erbB-2 oncogene. There was no difference in the VDR genotype between cancer and normal mucosal cells. Coexpression of erbB-2, pan-ras, p53 and EGFR internal and external domains was significantly higher in cancer cells than in normal mucosa. There was no significant correlation between VDR genotypes and age, gender, tumor infiltration depth, number and site of lymph node metastases and lymphatic or blood vessel infiltration. The VDR genotype alone did not influence survival. Overexpression of erbB-2 and EGFR was associated with a poor prognosis. In patients expressing only one oncogene in cancer cells, the presence of the VDR B allele showed a tendency to a poor prognosis. In conclusion, VDR gene BsmI polymorphism might affect the development and prognosis of rectal cancer by influencing erbB-2 oncogene expression.
Asunto(s)
Receptor ErbB-2/genética , Receptores de Calcitriol/genética , Neoplasias del Recto/genética , Adulto , Anciano , Anciano de 80 o más Años , Cartilla de ADN , Receptores ErbB/análisis , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Reacción en Cadena de la Polimerasa/métodos , Polimorfismo de Longitud del Fragmento de Restricción , Receptor ErbB-2/análisis , Receptores de Calcitriol/análisis , Neoplasias del Recto/química , Proteína p53 Supresora de Tumor/análisis , Regulación hacia Arriba , Proteínas ras/análisisRESUMEN
The Na+/K(+)-ATPase activity and expression of mRNAs encoding alpha and beta subunits of the enzyme were examined in rat myometrium at different stages of pregnancy. The enzyme activity appeared to increase during the pregnancy and reached the highest value at the 17th day. Northern blot analysis of total RNA isolated from the same myometrial samples shows the expressions of alpha 1, alpha 3 and beta mRNAs. A2 mRNA was not detectable. By the progression of pregnancy until the 17th day the expression of all the three kinds of mRNA increased. The change in the abundance of mRNA-beta was much more higher (12-fold) than that of mRNA-alpha 1 and -alpha 3 (4 and 2.5-fold, respectively). Furthermore, the expression of mRNA-beta sharply decreased after the 17th day, while the level of alpha subunits mRNAs barely changed. We conclude that transcriptional regulation of the Na+/K(+)-ATPase subunits could be different during this physiological process.
