Data on adenomatous polyposis coli reported by researchers at Columbia University
2009 JUL 6 - (NewsRx.com) -- "The majority of colorectal tumors are aneuploid because of the underlying chromosome instability (CIN) phenotype, in which a defective mitotic checkpoint is implicated. Adenomatous polyposis coli (APC), a tumor suppressor gene that is commonly mutated in colon cancers, has been suggested in causing CIN; however, the molecular mechanism remains unresolved," investigators in the United States report. "In this study, we report an interaction of tumor-associated N-terminal APC fragments (N-APC) with Mad2, an essential mitotic checkpoint protein, providing a direct molecular support for linking APC mutations to the generation of CIN. N-APC interacts with Mad2 in Xenopus egg extracts, colon cancer cells, and in vitro with purified components. The interaction between N-APC and Mad2 decreases the soluble pool of Mad2, which is essential for Mad2 cycling and releasing from unattached kinetochores to produce a diffusible ''wait anaphase'' signal. Addition of such an N-APC mutant of egg extracts inactivates the mitotic checkpoint," wrote J.Y. Zhang and colleagues, Columbia University. The researchers concluded: "Expressing a tumor-associated N-APC mutant in mammalian cells with an intact mitotic checkpoint produces premature anaphase onset with missegregated chromosomes.." Zhang and colleagues published their study in Molecular Biology of the Cell (Oncogenic Adenomatous Polyposis Coli Mutants Impair the Mitotic Checkpoint through Direct Interaction with Mad2. Molecular Biology of the Cell, 2009;20(9):2381-2388). For additional information, contact Y.H. Mao, Columbia University, Dept. of Pathology & Cell Biology, 630 W 168th St., New York City, NY 10032, USA. The publisher of the journal Molecular Biology of the Cell can be contacted at: American Society Cell Biology, 8120 Woodmont Avenue, Ste. 750, Bethesda, MD 20814-2755, USA. Keywords: United States, New York, Adenomatous Polyposis Coli, Colon Cancer, Colon Carcinoma, Colorectal, Endocrinology, Gastroenterology, Genetics, Oncology, Tumor Suppression, Columbia University. This article was prepared by Clinical Oncology Week editors from staff and other reports. Copyright 2009, Clinical Oncology Week via NewsRx.com.
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