RESUMO
Bladder cancer is the most frequent cancer of the urinary system. Fibroblast growth factor receptors (FGFR) belong to the tyrosine kinase family and have important roles in cell differentiation and proliferation and embryogenesis. FGFR3 is located on chromosome 4p16.3, and missense mutations of FGFR3 are associated with autosomal dominant human skeletal disorders and have some oncogenic effects. We examined the incidence of FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C, and in exon 10, G372C and T375C, and their correlation with clinical-pathological parameters in bladder carcinoma patients. Fifty-six paraffin-embedded specimens of transitional cell carcinoma of the urinary bladder were included in this study. Analysis of FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C, and in exon 10, G372C and T375C, was performed by PCR-restriction fragment length polymorphism (RFLP) analysis and DNA sequencing. FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C, and in exon 10, G372C and T375C, were detected in 33 of the 56 patients (heterozygous mutant). Among the 56 transitional cell carcinomas, missense point mutations were detected in seven of them at codon A248C, 28 of them at codon S249C, and three of them at codon T375C, similar to data from previous reports. When the results of the FGFR3 thanatophoric dysplasia mutations located in exon 7, A248C and S249C and in exon 10, G372C and T375C, were analyzed one by one or as a group, despite the findings of previous research reports, our data suggest that these mutations are detected homogenously regardless of the tumor classification and tumor grade.
Assuntos
Carcinoma de Células de Transição/genética , Receptor Tipo 3 de Fator de Crescimento de Fibroblastos/genética , Neoplasias da Bexiga Urinária/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células de Transição/epidemiologia , Carcinoma de Células de Transição/patologia , Códon , Éxons , Feminino , Estudos de Associação Genética , Genótipo , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Mutação , Estadiamento de Neoplasias , Displasia Tanatofórica/genética , Neoplasias da Bexiga Urinária/epidemiologia , Neoplasias da Bexiga Urinária/patologiaRESUMO
Up-regulated gene 4 (URG4), stimulated by HBxAg, is a novel gene located on chromosome 7 (7p13). The full-length URG4 clone is 3.607 kb and encodes a polypeptide of 922 amino acids, with a molecular weight of 104 kDa (GeneID: 55665). It promotes cell growth, growth factor-independent survival, and anchorage-independent growth in HepG2 cells, and it accelerates tumor formation in nude mice. Hence, URG4 may be a natural effector of HBxAg and a putative oncogene that contributes to multi-step hepatocarcinogenesis. Cyclin D1 is frequently over-expressed in hepatocellular carcinoma, exhibiting a number of malignant phenotypes. We found that down-regulation of URG4 through RNA interference-mediated silencing suppressed cell proliferation in HepG2 cells. Over-expression of URG4 up-regulated cyclin D1 mRNA expression, whereas RNA interference-mediated URG4 silencing diminished cyclin D1 mRNA expression in HepG2 cells. The data suggest that URG4 may play an important role in the development of hepatocellular carcinoma by partially regulating the expression of cyclin D1 and has potential for use as a therapeutic target for hepatocellular carcinoma.