Molecular alterations of E-cadherin gene: possible role in human bladder carcinogenesis.статья из журнала
Аннотация: E-cadherin is a transmembrane glycoprotein which mediates a calcium dependent homophilic interaction among epithelial cells. The altered expression and gene mutations of E-cadherin adhesion molecule have been frequently observed in various tumors. Several invasive carcinomas showed cell-cell adhesion loss although the tumor cells expressed considerable amounts of E-cadherin protein. The purpose of this study was to evaluate the role of E-cadherin gene alterations in genesis and progression of bladder carcinoma by mutation analysis of coding region, expression analysis and microsatellite instability at E-cadherin chromosome locus. We analyzed 30 bladder carcinoma (28 transitional and 2 squamous cell carcinoma) at different stage and grade. The mutation analysis showed that in one case there was a presence of a point mutation at codon 846 that consisted of a G (AGC) to C (ACC) transversion resulting in the replacement of R to T. In another sample the sequence analysis revealed a same-sense mutation at the codon 785 (AAC - AAT). The study of E-cadherin mRNA by Northern blot analysis showed that there were no differences of mRNA levels between tumor and normal mucosa samples. We noted that invasive and anaplastic tumors showed a trend to loss of expression, even if we did not find any statistically significant differences. The microsatellite analysis showed the presence of genomic instability in proximity of the E-cadherin gene. Nine out of 30 (30%) specimens presented molecular alterations in at least one out of 2 loci (D16S260 and D16S301) analyzed. The comparison between microsatellite mutations and clinical-histopathological parameters revealed a higher number of alterations in invasive respect to superficial tumors (p=0.014). On the other hand, there were no statistical differences regarding the correlation with pathological grade. These observations, which, nevertheless, need to be confirmed in a larger number of patients, suggest that alterations of E-cadherin gene may be related to pathobiology of bladder cancer development and clinical progression.
Год издания: 2000
Издательство: Spandidos Publishing
Источник: International Journal of Molecular Medicine
Ключевые слова: Cancer-related gene regulation, Wnt/β-catenin signaling in development and cancer, Kruppel-like factors research
Другие ссылки: International Journal of Molecular Medicine (HTML)
PubMed (HTML)
PubMed (HTML)
Открытый доступ: closed