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Activated cell cycle checkpoints in epirubicin-treated breast cancer cells studied by BrdUrd-flow cytometry

Author:
  • Ingrid Hedenfalk
  • Bo Baldetorp
  • Åke Borg
  • Stina Oredsson
Publishing year: 1997
Language: English
Pages: 321-327
Publication/Series: Cytometry
Volume: 29
Issue: 4
Document type: Journal article
Publisher: John Wiley & Sons

Abstract english

Genetic alterations, such as p53 mutations, may affect a tumour's response to chemotherapy. We have treated two human breast cancer cell lines that differ in p53 status with epirubicin in order to study if there are differences in cell cycle kinetic response. MCF-7 cells express wild-type p53, while SK-BR-3 cells express only a mutated form of p53. The transition of cells from one cell cycle stage to another was studied by a bromodeoxyuridine (BrdUrd)-flow cytometry (FCM) method. MCF-7 cells showed a block in the G1 phase after treatment with 50 nM epirubicin for 24 hours, in agreement with the actions of p53 at the G1 checkpoint. SK-BR-3 cells, on the other hand, progressed through the G1 checkpoint and were blocked in late S and G2 phases, presumably due to the activation of a later checkpoint. In addition, studies of the mRNA levels of p53 and its effector gene p21 revealed that although both cell lines expressed p53 mRNA, a marked difference in the mRNA levels of p21 was seen. A dramatic increase in the level of p21 mRNA was seen in epirubicin-treated MCF-7 cells, while no such increase was seen in SK-BR-3 cells.

Keywords

  • Neurology
  • breast cancer
  • epirubicin
  • p21
  • RNA
  • p53
  • bromodeoxyuridine
  • flow cytometry
  • cell cycle kinetics

Other

Published
  • ISSN: 0196-4763
Åke Borg
Åke Borg
E-mail: ake.borg [at] med.lu.se

Principal investigator

Oncology and Pathology, MV

+46 46 275 25 52

MV 404 C21B2

90

Project manager

Familial Breast Cancer

90

Professor

Oncology and Pathology, MV

MV 404 C21C2

90