Altered centrosome structure is associated with abnormal mitoses in human breast tumors

Wilma L. Lingle, Jeffrey L Salisbury

Research output: Contribution to journalArticle

155 Citations (Scopus)

Abstract

Centrosomes are the major microtubule organizing center in mammalian cells and establish the spindle poles during mitosis. Centrosome defects have been implicated in disease and tumor progression and have been associated with nullizygosity of the p53 tumor suppressor gene. In the present ultrastructural analysis of 31 human breast tumors, we found that centrosomes of most tumors had significant alterations compared to centrosomes of normal breast tissue. These alterations in included 1) supernumerary centrioles, 2) excess pericentriolar material, 3) disrupted centriole barrel structure, 4) unincorporated microtubule complexes, 5) centrioles of unusual length, 6) centrioles functioning as ciliary basal bodies, and 7) mispositioned centrosomes. These alterations are associated with changes in cell polarity, changes in cell and tissue differentiation, and chromosome missegregation through multipolar mitoses. Significantly, the presence of excess pericentriolar material was associated with the highest frequency of abnormal mitoses. Centrosome abnormalities may confer a mutator phenotype to tumors, occasionally yielding cells with a selective advantage that emerge and thrive, thus leading the tumor to a more aggressive state.

Original languageEnglish (US)
Pages (from-to)1941-1951
Number of pages11
JournalAmerican Journal of Pathology
Volume155
Issue number6
StatePublished - 1999

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Centrosome
Mitosis
Centrioles
Breast Neoplasms
Neoplasms
Microtubule-Organizing Center
Spindle Poles
Basal Bodies
Cell Polarity
Ciliary Body
Tumor Suppressor Genes
Microtubules
Disease Progression
Cell Differentiation
Breast
Chromosomes
Phenotype

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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Altered centrosome structure is associated with abnormal mitoses in human breast tumors. / Lingle, Wilma L.; Salisbury, Jeffrey L.

In: American Journal of Pathology, Vol. 155, No. 6, 1999, p. 1941-1951.

Research output: Contribution to journalArticle

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