Transient tyrosine phosphorylation of p34(cdc2) is an early event in radiation-induced apoptosis of prostate cancer cells

Natasha Kyprianou, Arvinder Bains, Juong G. Rhee

Research output: Contribution to journalArticlepeer-review

9 Scopus citations

Abstract

Previous studies have demonstrated that androgen-independent human prostate cancer cells undergo radiation-induced apoptosis. The present study investigated the early events that trigger the apoptotic response of prostate cancer cells after exposure to ionizing irradiation. METHODS. Human prostate cancer cells (PC-3) were exposed to single doses of ionizing irradiation, and the immediate protein phosphorylation events were temporally correlated with induction of apoptosis. Apoptosis among the irradiated cell populations was evaluated using the fluorescein-terminal transferase assay. RESULTS. The kinetics of phosphorylation of a Mr 34,000 substrate followed a transient course: an initial increase was observed after 10 min postirradiation, reaching maximum levels by 60 min, and the protein subsequently underwent rapid dephosphorylation. Subsequent analysis revealed that the substrate for this tyrosine phosphorylation is the serine/threonine p34(cdc2) protein kinase, a cell cycle regulatory protein that controls cell entry into mitosis. This enhanced phosphorylation temporally preceded the radiation- induced apoptotic DNA fragmentation as detected by the terminal transferase technique. Arresting the cells in G0/G1 phase by pretreatment with suramin totally abrogated radiation-induced phosphorylation of p34(cdc2) protein at the tyrosine residue, indicating that this posttranslational modification occurs in cell populations that escape G2 arrest and undergo apoptosis in response to radiation. CONCLUSIONS. These results suggest that a rapid and transient phosphorylation of a protein that controls mitotic progression precedes and potentially triggers radiation-induced apoptosis in prostate cancer cells.

Original languageEnglish
Pages (from-to)266-271
Number of pages6
JournalProstate
Volume32
Issue number4
DOIs
StatePublished - 1 Sep 1997
Externally publishedYes

Keywords

  • Prostate cancer
  • Radiation-induced apoptosis
  • Suramin
  • Tyrosine phosphorylation

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