hMSH6 deficiency and inactivation of the alpha E-catenin invasion-suppressor gene in HCT-8 colon cancer cells

Transition from an epithelioid (E) to a round (R) morphotype, in the human colon cancer cell line HCT-8, is associated with loss or truncation of alph a E-catenin and acquisition of invasiveness in organ culture. In E clones, like in parental HCT-8 cells, one allele of the alpha E-catenin gene (CTNNA 1) is mutated. HCT-8 cells have also a 'Microsatelite Instability-High' (MS I-H) phenotype presumably due to a mutated hMSH6 gene. Fusion of E type cel ls doubles the wild type CTNNA1 alleles and prevents the loss of alpha E-ca tenin. Introduction of an extra chromosome 2, carrying a wild type hMSH6 ge ne, restores post-replicative mismatch repair and also prevents the frequen t inactivation of the remaining wild type CTNNA1 allele.