UMMS Affiliation

Department of Pathology; Program in Molecular Medicine

Date

9-10-1998

Document Type

Article

Subjects

Antigens; Centrosome; Chromosome Aberrations; Fluorescent Antibody Technique; Humans; Immunoenzyme Techniques; Neoplasms; Tumor Cells, Cultured

Disciplines

Genetics and Genomics | Genetic Structures | Medical Molecular Biology | Medical Pathology | Oncology

Abstract

Genetic instability is a common feature of many human cancers. This condition is frequently characterized by an abnormal number of chromosomes, although little is known about the mechanism that generates this altered genetic state. One possibility is that chromosomes are missegregated during mitosis due to the assembly of dysfunctional mitotic spindles. Because centrosomes are involved in spindle assembly, they could contribute to chromosome missegregation through the organization of aberrant spindles. As an initial test of this idea, we examined malignant tumors for centrosome abnormalities using antibodies to the centrosome protein pericentrin. We found that centrosomes in nearly all tumors and tumor-derived cell lines were atypical in shape, size, and composition and were often present in multiple copies. In addition, virtually all pericentrin-staining structures in tumor cells nucleated microtubules, and they participated in formation of disorganized mitotic spindles, upon which chromosomes were missegregated. All tumor cell lines had both centrosome defects and abnormal chromosome numbers, whereas neither was observed in nontumor cells. These results indicate that centrosome defects are a common feature of malignant tumors and suggest that they may contribute to genetic instability in cancer.

Rights and Permissions

Citation: Cancer Res. 1998 Sep 1;58(17):3974-85.

Related Resources

Link to article in PubMed

Journal Title

Cancer research

PubMed ID

9731511

 
 

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