HOMEPRODUCTSSERVICESCOMPANYCONTACTFAQResearchDictionaryPharmaMobileSign Up FREE or Login

G(1) and G(2) cell-cycle arrest following microtubule depolymerization in human breast cancer cells.

Abstract
Microtubule-depolymerizing agents are widely used to synchronize cells, screen for mitotic checkpoint defects, and treat cancer. The present study evaluated the effects of these agents on normal and malignant human breast cell lines. After treatment with 1 microM nocodazole, seven of ten breast cancer lines (type A cells) arrested in mitosis, whereas the other three (type B cells) did not. Similar effects were observed with 100 nM vincristine or colchicine. Among five normal mammary epithelial isolates, four exhibited type A behavior and one exhibited type B behavior. Further experiments revealed that the type B cells exhibited a biphasic dose-response curve, with mitotic arrest at low drug concentrations (100 nM nocodazole or 6 nM vincristine) that failed to depolymerize microtubules and a p53-independent p21(waf1/cip1)-associated G(1) and G(2) arrest at higher concentrations (1 microM nocodazole or 100 nM vincristine) that depolymerized microtubules. Collectively, these observations provide evidence for coupling of premitotic cell-cycle progression to microtubule integrity in some breast cancer cell lines (representing a possible "microtubule integrity checkpoint") and suggest a potential explanation for the recently reported failure of some cancer cell lines to undergo nocodazole-induced mitotic arrest despite intact mitotic checkpoint proteins.
AuthorsApril L Blajeski, Vy A Phan, Timothy J Kottke, Scott H Kaufmann
JournalThe Journal of clinical investigation (J Clin Invest) Vol. 110 Issue 1 Pg. 91-9 (Jul 2002) ISSN: 0021-9738 [Print] United States
PMID12093892 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, P.H.S.)
Chemical References
  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins
  • Vincristine
  • Paclitaxel
  • Nocodazole
  • Colchicine
Topics
  • Breast Neoplasms (metabolism, pathology)
  • Colchicine (pharmacology)
  • Cyclin-Dependent Kinase Inhibitor p21
  • Cyclins (metabolism)
  • Dose-Response Relationship, Drug
  • Female
  • G1 Phase (drug effects)
  • G2 Phase (drug effects)
  • Humans
  • Microtubules (drug effects)
  • Nocodazole (administration & dosage, pharmacology)
  • Paclitaxel (pharmacology)
  • Tumor Cells, Cultured
  • Vincristine (administration & dosage, pharmacology)

Join CureHunter, for free Research Interface BASIC access!

Take advantage of free CureHunter research engine access to explore the best drug and treatment options for any disease. Find out why thousands of doctors, pharma researchers and patient activists around the world use CureHunter every day.
Realize the full power of the drug-disease research network!


Choose Username:
Email:
Password:
Verify Password: