Functional analysis of the mismatch repair system in bladder cancer.

摘要: In bladder cancer the observed microsatellite instability indicates that mismatch repair deficiency could be a frequently involved factor in progression. To investigate this hypothesis we analysed extracts of seven cell lines and, as novel approach, five clinical samples for activity. We found one line (T24) and three had reduced capacity, measured to ~20% or less. The T24 extract was unable G-G showed 2-base loop, consistent with diminished function MSH2-MSH6 heterodimer. functional assay combined measurement mutation frequency, analysis, sequencing, MTT assay, immunohistochemical analysis RT-PCR genes MSH2, MSH3, MSH6, PMS1, PMS2 MLH1. A >7-fold relative increase frequency compared fully system. Neither instability, loss nor gene mutations were detected. However, mRNA levels did detect changes ratio expression Mut S L homologues. lowest MSH6 level tested. Identical seventeen (normal urothelium, 7; pTa low stage, 5; pT1-4 high 5) indicated significant change between MSH3/MSH6 (P< 0.004), MSH2/MSH3 0.012) PMS2/MLH1 P< 0.005, stage tumours normal urothelium tumours. Collectively, data suggest imbalanced lead partial activity is associated invasive cancer. © 2001 Cancer Research Campaign http://www.bjcancer.com