MLH1 function is context dependent in colorectal cancers

Background and aimsLoss of mismatch repair (MMR) function in sporadic colorectal cancer occurs most commonly because of inactivation of MLH1, and it causes an increase in mutation rate. However, it is uncertain whether loss of MMR alters any other cellular function. The aim of this study was to investigate the role of MMR in regulating cell numbers and apoptosis.MethodsMLH1 protein levels were manipulated by (a) cloning and forcibly expressing MLH1 in HCT116 (a cell line with MLH1 mutation) and RKO (a cell line with MLH1 silencing), and (b) knockdown of MLH1 in SW480 (a cell line with normal MMR function). Cell number and apoptotic bodies were measured in standard and ‘high stress’ (ie, after staurosporine exposure) conditions.ResultsRestoration of MLH1 function in HCT116 and RKO resulted in increased cell number (p