Modulation of mitogen-activated protein kinases and phosphorylation of Bcl-2 by vinblastine represent persistent forms of normal fluctuations at G2-M1

Meiyun Fan, L. Du, A. A. Stone, K. M. Gilbert, T. C. Chambers

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Abstract

Microtubule inhibitors, widely used in cancer chemotherapy, induce G2-M arrest and apoptosis and have in common the ability to stimulate Raf-1/Bcl-2 phosphorylation and activate c-Jun NH2-terminal protein kinase (JNK). These signal transduction pathways are thought to be activated in response to microtubule damage to promote apoptosis. However, Bcl-2 phosphorylation has been reported to occur at G2-M in nonapoptotic cells, raising the possibility that this and perhaps other signaling pathways altered by microtubule inhibitors reflect perturbations of normal mitotic events. In this study, we sought to test this hypothesis. We show that Bcl-2 phosphorylation and JNK activation, as well as extracellular response kinase and p38 inactivation, occur not only in response to vinblastine but also as discrete transient events at G2-M phase in untreated synchronized KB-3 cells. Thus, modulation of these pathways is not a response to microtubule damage; rather they occur normally at G2-M, and it is the extent, duration, and/or irreversible nature of the signals that distinguish a preapoptotic cell from one destined to divide. These findings provide novel insight into the relationship between mitotic and apoptotic signaling and the mechanism of action of antimitotic drugs.

Original languageEnglish (US)
Pages (from-to)6403-6407
Number of pages5
JournalCancer Research
Volume60
Issue number22
StatePublished - Dec 7 2000

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Vinblastine
Mitogen-Activated Protein Kinases
Microtubules
Phosphorylation
JNK Mitogen-Activated Protein Kinases
Protein Kinases
Apoptosis
Antimitotic Agents
KB Cells
G2 Phase
Cell Division
Signal Transduction
Phosphotransferases
Drug Therapy
Neoplasms

All Science Journal Classification (ASJC) codes

  • Oncology
  • Cancer Research

Cite this

Modulation of mitogen-activated protein kinases and phosphorylation of Bcl-2 by vinblastine represent persistent forms of normal fluctuations at G2-M1. / Fan, Meiyun; Du, L.; Stone, A. A.; Gilbert, K. M.; Chambers, T. C.

In: Cancer Research, Vol. 60, No. 22, 07.12.2000, p. 6403-6407.

Research output: Contribution to journalArticle

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AU - Gilbert, K. M.

AU - Chambers, T. C.

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