hMSH6 deficiency and inactivation of the alphaE-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 alphaE-catenin and acquisition of invasiveness in organ culture. In E clones, like in parental HCT-8 cells, one allele of the alphaE-catenin gene (CTNNA1) is mutated. HCT-8 cells have also a 'Microsatelite Instability-High' (MSI-H) phenotype presumably due to a mutated hMSH6 gene. Fusion of E type cells doubles the wild type CTNNA1 alleles and prevents the loss of alphaE-catenin. Introduction of an extra chromosome 2, carrying a wild type hMSH6 gene, restores post-replicative mismatch repair and also prevents the frequent inactivation of the remaining wild type CTNNA1 allele.
Department of Radiotherapy and Nuclear Medicine, Ghent University Hospital, Belgium.
S J
SJ
Vermeulen
P R
PR
Debruyne
G
G
Marra
F P
FP
Speleman
P
P
Boukamp
J
J
Jiricny
A P
AP
Cuthbert
R F
RF
Newbold
F H
FH
Nollet
F M
FM
van Roy
M M
MM
Mareel
D000483:Alleles; D000818:Animals; D020137:Base Pair Mismatch; D002459:Cell Fusion; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003598:Cytoskeletal Proteins / Q000096:biosynthesis / Q000235:genetics*; D004260:DNA Repair; D004268:DNA-Binding Proteins / Q000172:deficiency* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D020868:Gene Silencing / Q000502:physiology*; D016147:Genes, Tumor Suppressor / Q000235:genetics*; D006801:Humans; D051379:Mice; D010641:Phenotype; D011123:Polyploidy; D014162:Transfection; D014407:Tumor Cells, Cultured; D051178:alpha Catenin
C495273:CTNNA1 protein, human; C495272:Ctnna1 protein, mouse; D003598:Cytoskeletal Proteins; D004268:DNA-Binding Proteins; C094443:G-T mismatch-binding protein; C102997:Msh6 protein, mouse; D051178:alpha Catenin