Human Cancer Cell Lines Deficient in the CDC4 Gene

To assess the role of CDC4 in genetic instability, we generated cells that lack functional CDC4 genes. An abnormal chromosome number (aneuploidy) is a hallmark of human cancer, recognized for nearly a century. However, the mechanism(s) responsible for aneuploidy has remained elusive. Here we report the identification of hCDC4/Fbw7/Archipelago mutations in human colorectal adenomas and 12% of colorectal carcinomas and the functional characterization of hCDC4 through targeted disruption of the gene in karyotypically stable colorectal cancer cells. Inactivation of the hCDC4 gene resulted in a striking phenotype associated with micronuclei and chromosomal instability. This instability appeared to be due to a defect in the execution of metaphase and subsequent chromosome transmission and implicates hCDC4 in mitotic regulation Description (Set) Proposed Use (Set) Isogenic cell lines with or without intact CDC4 genes are valuable reagents for studying aneuploidy in human cancers.. They can also be used for identifying novel small molecules that are dependent on genetic instability to induce apoptosis in human cancer cells, which can potentially be used as chemotherapeutic or chemopreventive agents.

Inventor(s): Vogelstein, Bert

Type of Offer: Licensing

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