Computer modeling implicates stem cell overproduction in colon cancer initiation.

Boman, B M; Fields, J Z; Bonham-Carter, O; Runquist, O A

Boman, B M; Fields, J Z; Bonham-Carter, O; Runquist, O A.

Afiliación

Boman BM; Division of Genetic and Preventive Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania 19107, USA. Bruce.Boman@mail.tju.edu

Cancer Res ; 61(23): 8408-11, 2001 Dec 01.

Article en En | MEDLINE | ID: mdl-11731419

RESUMEN

On the basis of our investigation of the premalignant crypt phenotype in familial adenomatous polyposis patients, the hypothesis is developed that tumor initiation in the colon is caused by crypt stem cell overproduction. A novel kinetic model for the colonic crypt was used to investigate how the earliest tissue abnormality (altered crypt labeling index) arises in these patients who have a mutant APC genotype. Only an increase in crypt stem cell number, not changes in the rate of cell cycle proliferation, differentiation, or apoptosis of the non-stem cell population, simulated this abnormality. This suggests that APC regulates the number of stem cells in the colonic crypt and when the cells become mutant, an expansion of the crypt stem cell population results.

Asunto(s)

Poliposis Adenomatosa del Colon/patología; Neoplasias del Colon/patología; Modelos Biológicos; Células Madre/patología; Poliposis Adenomatosa del Colon/genética; Neoplasias del Colon/genética; Simulación por Computador; Humanos; Lesiones Precancerosas/genética; Lesiones Precancerosas/patología

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Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Células Madre / Neoplasias del Colon / Poliposis Adenomatosa del Colon / Modelos Biológicos Límite: Humans Idioma: En Revista: Cancer Res Año: 2001 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos

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