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Transient tyrosine phosphorylation of p34 cdc2 is an early event in radiation‐induced apoptosis of prostate cancer cells
Author(s) -
Kyprianou Natasha,
Bains Arvinder,
Rhee Juong G.
Publication year - 1997
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/(sici)1097-0045(19970901)32:4<266::aid-pros6>3.0.co;2-h
Subject(s) - apoptosis , phosphorylation , tyrosine phosphorylation , biology , cancer research , cell cycle , prostate cancer , dna fragmentation , protein phosphorylation , mitosis , cancer cell , programmed cell death , microbiology and biotechnology , protein kinase a , cancer , biochemistry , genetics
BACKGROUND 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 G 0 /G 1 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 G 2 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. Prostrate 32:266–271, 1997. © 1997 Wiley‐Liss, Inc.