Forced expression of the tumor suppressor adenomatosis polyposis coli protein induces disordered cell migration in the intestinal epithelium.

Mutations of the human adenomatosis polyposis coli (APC) gene are associated with the development of familial as well as sporadic intestinal neoplasia. To examine the in vivo function of APC, 129/Sv embryonic stem (ES) cells were transfected with DNA encoding the wild-type human protein under the control of a promoter that is active in all four of the small intestine's principal epithelial lineages during their migration-associated differentiation. ES-APC cells were then introduced into C57BL/6-ROSA26 blastocysts. Analyses of adult B6-ROSA26<-->129/Sv-APC chimeric mice revealed that forced expression of APC results in markedly disordered cell migration. When compared with the effects of forced expression of E-cadherin, the data suggest that APC-catenin and E-cadherin-catenin complexes have opposing effects on intestinal epithelial cell movement/adhesiveness; augmentation of E-cadherin-beta-catenin complexes produces a highly ordered, "adhesive" migration, whereas augmentation of APC-beta-catenin complexes produces a disordered, nonadhesive migratory phenotype. We propose that APC mutations may promote tumorigenesis by increasing the relative activity of cadherin-catenin complexes, resulting in enhanced adhesiveness and functional anchorage of initiated cells within the intestinal crypt. Our studies also indicate that chimeric mice generated from B6-ROSA26 blastocysts and genetically manipulated ES cells should be useful for auditing gene function in the gastrointestinal tract and in other tissues.

Three Essays on the Economics of International Migration [electronic resource].

requirements for Filipino performing artists, effectively closing this migration channel. I employ a difference-in-differences estimation strategy using the share of performing artists at baseline in each Philippine province as a continuous policy variable. International migration falls in response to the policy change by 1.2%. The effect on international migration is larger than the policy change itself would suggest, indicating the importance of spillovers across migrant occupations. Domestically, more children are employed, and adults are more likely to be unemployed or engaged in short-term work.

Unauthorized migration : an economic development response : executive summary : report of the Commission for the Study of International Migration and Cooperative Economic Development.

"July 1990."

Unauthorized migration : addressing the root causes : hearings before the Commission for the Study of International Migration and Cooperative Economic Development, 1987-1990

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