Genotype-phenotype correlation in murine Apc mutation: Differences in enterocyte migration and response to sulindac

Najjia N. Mahmoud, Robyn T. Bilinski, Matthew R. Churchill, Winfried Edelmann, Raju Kucherlapati, Monica M. Bertagnolli

Research output: Contribution to journalArticle

56 Scopus citations

Abstract

The adenomatous polyposis coli (APC) gene product mediates coordinated cell growth in the intestinal mucosa. In humans, germ-line mutations of APC are associated with colorectal carcinogenesis, a process that varies in severity depending on the length of the protein resulting from the mutant allele. In a previous study of the C57BL/6J-Min/+ (Min/+) mouse, we found that the protein fragment resulting from truncation at codon 850 of murine Apc was associated with changes in enterocyte migration, proliferation, apoptosis, and β-catenin expression. This effect was reversed upon treatment of Min/+ mice with the chemopreventive drug sulindac sulfide. In this study, we measured enterocyte migration in the Apc1638N mouse, an animal with an Apc mutation that yields no detectable APC protein. We found no difference in enterocyte migration, proliferation, apoptosis, or β-catenin levels in the Apc1638N mouse when compared to wild-type littermates bearing two normal Apc alleles. Furthermore, administration of sulindac sulfide to Apc1638N mice did not alter enterocyte migration. These observations suggest that a dominant negative effect altering cell migration is exerted by the truncated APC protein present in the Min/+ mouse. These data also suggest that the effectiveness of chemopreventive agents in preventing Apc-related tumor formation may depend on which type of mutation is present.

Original languageEnglish (US)
Pages (from-to)353-359
Number of pages7
JournalCancer Research
Volume59
Issue number2
StatePublished - Jan 16 1999

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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    Mahmoud, N. N., Bilinski, R. T., Churchill, M. R., Edelmann, W., Kucherlapati, R., & Bertagnolli, M. M. (1999). Genotype-phenotype correlation in murine Apc mutation: Differences in enterocyte migration and response to sulindac. Cancer Research, 59(2), 353-359.