RGD Reference Report - Centrosome amplification and overexpression of aurora a are early events in rat mammary carcinogenesis. - Rat Genome Database

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Centrosome amplification and overexpression of aurora a are early events in rat mammary carcinogenesis.

Authors: Goepfert, TM  Adigun, YE  Zhong, L  Gay, J  Medina, D  Brinkley, WR 
Citation: Goepfert TM, etal., Cancer Res 2002 Jul 15;62(14):4115-22.
RGD ID: 619665
Pubmed: PMID:12124350   (View Abstract at PubMed)

The cells of many solid tumors have been found to contain supernumerary centrosomes, a condition known as centrosome amplification. Centrosome amplification, accompanied by the overexpression of an associated kinase, Aurora A (AurA), has been implicated in mechanisms leading to mitotic spindle aberrations, aneuploidy, and genomic instability. Using a well-established rat mammary model favorable for experimental carcinogenesis, we analyzed centrosome amplification as a cellular marker for early stages of transformation and its regulation by the kinase ratAurA. Parity or treatment with estrogen and progesterone conferred resistance to tumorigenesis, as well as to overexpression of ratAurA and to centrosome amplification. ratAurA, cloned from a rat mammary gland cDNA library, is a bona fide Ser/Thr kinase, and sequence comparison demonstrated high homology to members of the entire AurA kinase family. Using immunocytochemical localization with confocal microscopy, we found ratAurA to be localized at the centrosome in normal and neoplastic tissues of the rat mammary gland. Normal ductal epithelium and stromal cells displayed an expected complement of one to two centrosomes/cell, whereas comparable cells in methylnitrosourea-treated animals displayed significantly elevated centrosome numbers. In tumors, 46% of cells showed more than two centrosomes/cell, and ratAurA expression levels coincided with higher centrosome numbers. Both centrosome numbers and ratAurA expression were permanently elevated. Centrosome amplification was found to occur at a very early, premalignant stage prior to detectable lesions after treatment with methylnitrosourea, a condition that was not detected in mammary glands of rats made refractory to the carcinogen via pregnancy or estrogen and progesterone treatment. Our results indicate that hormones influence kinase expression, and progesterone had the major effect on ratAurA expression levels. Cumulatively, these results suggest that ratAurA overexpression and centrosome amplification were linked to tumor development and progression and may serve as early markers in tumorigenesis.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AurkaRatprotein phosphorylation  IDA  RGD 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AurkaRatcentrosome  IDA  RGD 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
AurkaRatprotein serine/threonine kinase activity  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Aurka  (aurora kinase A)


Additional Information