Centrosome defects can account for cellular and genetic changes that characterize prostate cancer progression

Citation
Ga. Pihan et al., Centrosome defects can account for cellular and genetic changes that characterize prostate cancer progression, CANCER RES, 61(5), 2001, pp. 2212-2219
Citations number
47
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER RESEARCH
ISSN journal
0008-5472 → ACNP
Volume
61
Issue
5
Year of publication
2001
Pages
2212 - 2219
Database
ISI
SICI code
0008-5472(20010301)61:5<2212:CDCAFC>2.0.ZU;2-I
Abstract
Factors that determine the biological and clinical behavior of prostate can cer are largely unknown. Prostate tumor progression is characterized by cha nges in cellular architecture, glandular organization, and genomic composit ion. 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 ar e structurally and numerically abnormal in the majority of prostate carcino mas. Centrosome abnormalities increase with increasing Gleason grade and wi th increasing levels of genomic instability. Selective induction of centros ome abnormalities by elevating levels of the centrosome protein pericentrin in prostate epithelial cell lines reproduces many of the phenotypic charac teristics of high-grade prostate carcinoma. Cells that transiently or perma nently express pericentrin exhibit severe centrosome and spindle defects, c ellular disorganization, genomic instability, and enhanced growth in soft a gar, On the basis of these observations, we propose a model in which centro some dysfunction contributes to the progressive loss of cellular and glandu lar architecture and increasing genomic instability that accompany prostate cancer progression, dissemination, and lethality.