Paclitaxel-induced apoptosis is associated with expression and activation of c-Mos gene product in human ovarian carcinoma SKOV3 cells

Yi He Ling, Yandan Yang, Carmen Tornos, Balraj Singh, Roman Perez-Soler

Research output: Contribution to journalArticle

37 Citations (Scopus)

Abstract

The c-Mos gene product is a component of the cytostatic factor and, as such, stabilizes the maturation-promoting factor causing cell-cycle blockade at metaphase II in unfertilized eggs. The potential role of c-Mos in regulating cell-cycle progression and cell death in somatic cells remains unknown. We studied whether paclitaxel-induced M-phase arrest and apoptosis are associated with c-Mos gene expression and activation in SKOV3 ovarian carcinoma cells. The first cellular effect observed with continuous exposure to 50 ng/ml paclitaxel (ID50) was mitotic arrest with an increase in the accumulation of cyclin B1 and stimulation of cdc2/cyclin B1 kinase in a time- dependent manner during a 36-h incubation. DNA fragmentation determined by agarose gel electrophoresis and quantitation of [3H]thymidine-prelabeled genomic DNA was a later event, first detected at 24 h and peaking at 48 h (later time points were not studied). Induction of the c-Mos gene expression and activation were determined by Western blot analysis, immunoprecipitation using a polyclonal anti-mos antibody, reverse transcription-PCR assay, and 32P-ATP incorporation into c-Mos protein or the substrate of glutathione S- transferase mitogen-activated protein kinase kinase, respectively. Both induction and activation were clearly detected after 24 h of exposure to paclitaxel concentrations of >50 ng/ml, coinciding with drug-induced apoptosis. Mitogen-activated protein kinase activation preceded c-Mos gene induction. Paclitaxel-induced cMos gene expression was completely abrogated by cycloheximide and actinomycin D. Mos gene expression was also induced in SKOV3 cells that were treated with vinblastine but not in those that were treated with camptothecin, etoposide, or cisplatin. We concluded that tubulin-disturbing agents induce c-Mos gene expression and activation in SKOV3 ovarian carcinoma cells and that such an effect occurs after mitotic blockade and coincides with drug-induced apoptosis.

Original languageEnglish (US)
Pages (from-to)3633-3640
Number of pages8
JournalCancer Research
Volume58
Issue number16
StatePublished - Aug 15 1998
Externally publishedYes

Fingerprint

mos Genes
Paclitaxel
Apoptosis
Carcinoma
Proto-Oncogene Proteins c-mos
Gene Expression
Transcriptional Activation
Cyclin B1
Cell Cycle
Maturation-Promoting Factor
Camptothecin
Vinblastine
Agar Gel Electrophoresis
Mitogen-Activated Protein Kinase Kinases
Dactinomycin
DNA Fragmentation
Etoposide
Cycloheximide
Tubulin
Metaphase

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Paclitaxel-induced apoptosis is associated with expression and activation of c-Mos gene product in human ovarian carcinoma SKOV3 cells. / Ling, Yi He; Yang, Yandan; Tornos, Carmen; Singh, Balraj; Perez-Soler, Roman.

In: Cancer Research, Vol. 58, No. 16, 15.08.1998, p. 3633-3640.

Research output: Contribution to journalArticle

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