Altered centrosomes in ataxia-telangiectasia cells and rapamycin-treated Chinese hamster cells

Stefanie Bonatti, Marcella Simili, Pier Alberto Benedetti, Fabio Morandi, Paola Menichini, Renata Del Carratore, Roberta Barale, Angelo Abbondandolo

Research output: Contribution to journalArticlepeer-review

Abstract

Rapamycin induces chromosome malsegregation in mammalian cell lines and yeast. Previous studies indicate that the function impaired in ataxia-telangiectasia (A-T) patients is necessary for both the growth inhibition and the chromosome malsegregation induced by rapamycin, and that treating the non-tumorigenic Chinese hamster cell line CHEF/ 18 with rapamycin results in supernumerary centrosomes and multipolar spindles. In this paper we report that lymphoblastoid cell lines established from A-T patients as well as hamster A-T-like cells are more resistant to rapamycin than the respective normal cell lines. Two cell lines derived from Nijmegen Breakage Syndrome (NBS) patients, who have clinical symptoms similar to those of A-T but a different molecular defect, were not resistant to rapamycin. Both A-T lymphoblastoid cells and A-T-like fibroblasts had giant centrosomes formed by more than two areas of ã-tubulin-reacting material. Such giant centrosomes were also observed in CHEF/18 cells after prolonged treatment with rapamycin. Formation of giant centrosomes, possibly due to the coalescence of supernumerary centrosomes, was associated with increased aneuploidy in treated cells. Expression analysis of cell-cycle regulatory genes in rapamycin-treated human lymphoblastoid cells indicated that rapamycin decreased the expression of the tumor suppressor gene GADD45. The levels of RB, p21 and p53 mRNA were also decreased, although to a lesser extent. As rapamycin is often used as an immunosuppressant in pediatric transplant patients, these data indicate that caution should be taken, especially when the drug is given for prolonged periods of time.

Original languageEnglish
Pages (from-to)164-173
Number of pages10
JournalEnvironmental and Molecular Mutagenesis
Volume46
Issue number3
DOIs
Publication statusPublished - Oct 2005

Keywords

  • Aneuploidy
  • Ataxia-telangiectasia
  • Centrosomes
  • mTOR
  • Rapamycin

ASJC Scopus subject areas

  • Environmental Science(all)
  • Environmental Chemistry
  • Genetics
  • Genetics(clinical)
  • Toxicology
  • Health, Toxicology and Mutagenesis

Fingerprint Dive into the research topics of 'Altered centrosomes in ataxia-telangiectasia cells and rapamycin-treated Chinese hamster cells'. Together they form a unique fingerprint.

Cite this