UMMS Affiliation

Department of Pathology; Program in Molecular Medicine

Publication Date

3-31-2001

Document Type

Article

Subjects

Antigens; Centrosome; Disease Progression; Humans; Male; Phenotype; Prostatic Neoplasms

Disciplines

Cell Biology | Medical Cell Biology | Medical Genetics | Medical Molecular Biology | Medical Pathology | Oncology

Abstract

Factors that determine the biological and clinical behavior of prostate cancer are largely unknown. Prostate tumor progression is characterized by changes in cellular architecture, glandular organization, and genomic composition. These features are reflected in the Gleason grade of the tumor and in the development of aneuploidy. Cellular architecture and genomic stability are controlled in part by centrosomes, organelles that organize microtubule arrays including mitotic spindles. Here we demonstrate that centrosomes are structurally and numerically abnormal in the majority of prostate carcinomas. Centrosome abnormalities increase with increasing Gleason grade and with increasing levels of genomic instability. Selective induction of centrosome abnormalities by elevating levels of the centrosome protein pericentrin in prostate epithelial cell lines reproduces many of the phenotypic characteristics of high-grade prostate carcinoma. Cells that transiently or permanently express pericentrin exhibit severe centrosome and spindle defects, cellular disorganization, genomic instability, and enhanced growth in soft agar. On the basis of these observations, we propose a model in which centrosome dysfunction contributes to the progressive loss of cellular and glandular architecture and increasing genomic instability that accompany prostate cancer progression, dissemination, and lethality.

Rights and Permissions

Citation: Cancer Res. 2001 Mar 1;61(5):2212-9.

Related Resources

Link to article in PubMed

Journal/Book/Conference Title

Cancer research

PubMed ID

11280789

 
 

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