E-cadherin and adenomatous polyposis coli mutations are synergistic in intestinal tumor initiation in mice

R Smits ¹, P Ruiz , S Diaz-Cano

⁰Medical Genetics Center, Department of Human and Clinical Genetics, Leiden University Medical Center, Leiden, The Netherlands.

Gastroenterology +

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October 21, 2000

View abstract on PubMed

Summary

Introducing an E-cadherin mutation into Apc mouse models significantly increased intestinal and gastric tumor numbers, enhancing tumor initiation. This suggests E-cadherin plays a key role in early stages of Apc-driven tumorigenesis.

Area Of Science

Oncology
Molecular Biology
Genetics

Background

Adenomatous polyposis coli (APC) gene inactivation is an early event in intestinal tumor formation.
Loss of E-cadherin is typically associated with tumor progression.
Both APC and E-cadherin interact with beta-catenin in the Wnt signaling pathway.

Purpose Of The Study

To investigate the impact of reduced E-cadherin levels on Apc-driven tumor initiation and progression.
To determine if E-cadherin haploinsufficiency influences tumorigenesis by altering cell-adhesive functions.

Main Methods

Breeding Apc1638N mice with animals carrying a targeted E-cadherin knockout mutation.
Analyzing tumor numbers, grading, and staging in double heterozygous and Apc1638N control animals.
Performing loss of heterozygosity analysis at Apc and E-cadherin loci in tumors.

Main Results

Double heterozygous animals exhibited a 9-fold increase in intestinal and a 5-fold increase in gastric tumor numbers compared to Apc1638N controls.
Intestinal tumors showed no significant differences in grading and staging between the groups.
Loss of heterozygosity analysis revealed retention of the wild-type E-cadherin allele in all analyzed tumors, despite reduced E-cadherin staining.

Conclusions

E-cadherin mutation introduction in Apc1638N mice enhances Apc-driven tumor initiation.
Tumor progression was not significantly affected by the E-cadherin mutation in this model.
E-cadherin plays a critical role in the early stages of Apc-driven intestinal tumorigenesis.

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