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[Cancer Research 59, 353-359, January 1, 1999]
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[Cancer Research 59, 353-359, January 15, 1999]
© 1999 American Association for Cancer Research

Carcinogenesis

Genotype-Phenotype Correlation in Murine Apc Mutation: Differences in Enterocyte Migration and Response to Sulindac1

Najjia N. Mahmoud, Robyn T. Bilinski, Matthew R. Churchill, Winfried Edelmann, Raju Kucherlapati and Monica M. Bertagnolli2

The New York Hospital-Cornell Medical Center, New York, New York 10021 [N. N. M., R. T. B., M. R. C., M. M. B.]; Strang Cancer Prevention Center, New York, New York 10021 [M. M. B.]; and Albert Einstein College of Medicine of Yeshiva University, Bronx, New York 10461 [W. E., R. K.]

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 ß-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 ß-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.




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HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
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Cancer Epidemiology Biomarkers & Prevention Molecular Cancer Therapeutics
Molecular Cancer Research Cancer Prevention Research
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Annual Meeting Education Book Meeting Abstracts Online
Copyright © 1999 by the American Association for Cancer Research.