PARENT SESSION
1:30 PM to 3:30 PM
Tuesday, April 23, 2002
Poster Session 24 Signal Transduction
Room: Nevada Exhibition Center

(P29-283) PKCdelta Overexpression Enhances Radiation Sensitivity via ERK1/2 Activation and Abolishing the Radiation Induced G2/M Arrest.

Lee, Yun-Sil^*,1, Lee, Yoon-Jin¹, Dean, Nicholas², Lee, Su-Jae¹, Cho, Chul-Koo¹, ¹ Lab of Radiation Effect, Seoul, Korea² Department of Molecular Pharmacology, ISIS Pharmaceuticals, Carsbad, California

ABSTRACT-
Protein kinase C (PKC) has been widely implicated in regulation of cell growth/cell cycle progression and apoptosis. However, the role of PKCdelta in radiosenstivity and cell cycle regulation remain unclear. Overexpression of PKCdelta increased Ca²⁺-independent PKC activity without altering other PKC isoforms (PKCalpha, beta1, epsilon, and zeta), and extracellular regulated protein kinase (ERK)1/2 activity was also increased in PKCdelta specific manner. A clonogenic survival assay showed that PKCdelta overexpressed cells had more radiosensitivity and pronounced induction of apoptosis than control cells. Flow cytometric analysis revealed that PKCdelta made the cells escape from radiation induced-G2/M arrest. Moreover, p53 and p21 inductions by radiation were higher in PKCdelta overexpressed cells than control cells, and PKCdelta-mediated apoptosis was reduced, when radiation induced ERK1/2 activity was inhibited by PD98059. Furthermore, PKCdelta antisense and rottlerine, PKC inhibitor abrogated PKCdelta-mediated radiosensitivity and reduced ERK1/2 activity to the control vector level. These results demonstrated that PKCdelta overexpression enhanced radiation-induced apoptosis and radiosensitivity via ERK1/2 activation, thereby abolishing the radiation induced G2/M arrest and finally apoptosis.

KEYWORDS: PKCdelta, EKR1/2, Radiosensitivity, Apoptosis, G2/M phas