CDX2 does not suppress tumorigenicity in the human gastric cancer cell line MKN45.
CDX2 is a Drosophila caudal-related homeobox transcription factor that is expressed specifically in the intestine. In mice, ectopic expression of CDX2 in the gastric mucosa gives rise to intestinal metaplasia and in one model, gastric carcinoma. In humans, increased CDX2 expression is associated with gastric intestinal metaplasia and tubular adenocarcinomas. These patterns of expression have shown that CDX2 is important for the initiation of intestinal metaplasia in the gastric mucosa, but the role of CDX2 in established gastric cancer remains unclear. We sought to determine whether CDX2 contributes to tumorigenic potential in established gastric cancer. The CDX2 gene in MKN45 gastric carcinoma cells was disrupted using targeted homologous recombination. The resulting CDX2-/- cells are essentially identical to their parental cells, with the exception of CDX2 ablation. We found no significant differences in the proliferation of CDX2-/- cells compared to CDX2+/+ cells, in vitro or in vivo. Molecular analyses show that loss of CDX2 predominantly altered the expression of genes involved in intestinal glandular differentiation and adhesion. However, there were no microscopic differences in tumor differentiation. We conclude that disruption of CDX2 in MKN45 cells does not significantly affect their tumorigenic potential.
Dang
L H
LH
Division of Hematology/Oncology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109-0682, USA.
Chen
F
F
Knock
S A
SA
Huang
E H
EH
Feng
J
J
Appelman
H D
HD
Dang
D T
DT
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology*; D001483:Base Sequence; D000071616:CDX2 Transcription Factor; D002453:Cell Cycle; D002454:Cell Differentiation; D002455:Cell Division; D045744:Cell Line, Tumor; D017931:DNA Primers; D018398:Homeodomain Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation; D011995:Recombination, Genetic; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013274:Stomach Neoplasms / Q000473:pathology*
D000071616:CDX2 Transcription Factor; C491270:CDX2 protein, human; D017931:DNA Primers; D018398:Homeodomain Proteins