Combination of PTEN and {gamma}-Ionizing Radiation Enhances Cell Death and G{sub 2}/M Arrest Through Regulation of AKT Activity and p21 Induction in Non-Small-Cell Lung Cancer Cells

Journal Article · Tue Apr 01 04:00:00 EDT 2008 · International Journal of Radiation Oncology, Biology and Physics

DOI:https://doi.org/10.1016/j.ijrobp.2007.11.069· OSTI ID:21124167

Park, Jong Kuk; Jung, Hae-Yun; Park, Seon Ho; Kang, Seung Yi; Yi, Mi-Rang; Um, Hong Duck ^[1]

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1. Laboratory of Radiation Tumor Physiology, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

Purpose: To identify the role of phosphatase and tensin homolog deleted on chromosome 10 (PTEN) during {gamma}-ionizing radiation ({gamma}-IR) treatment for non-small-cell lung cancer cells. Methods and Materials: Wild-type PTEN or mutant forms of PTEN plasmids were transfected to construct stable transfectants of the NCI-H1299 non-small-cell lung cancer cell line. Combined effects of PTEN expression and IR treatment were tested using immunoblot, clonogenic, and cell-counting assays. Related signaling pathways were studied with immunoblot and kinase assays. Results: At steady state, stable transfectants showed almost the same proliferation rate but had different AKT phosphorylation patterns. When treated with {gamma}-IR, wild-type PTEN transfectants showed higher levels of cell death compared with mock vector or mutant transfectants, and showed increased G{sub 2}/M cell-cycle arrest accompanied by p21 induction and CDK1 inactivation. NCI-H1299 cells were treated with phosphosinositide-3 kinase (PI3K)/AKT pathway inhibitor (LY29002), resulting in reduced AKT phosphorylation levels. Treatment of NCI-H1299 cells with LY29002 and {gamma}-IR resulted in increased cell-cycle arrest and p21 induction. Endogenous wild-type PTEN-containing NCI-H460 cells were treated with PTEN-specific siRNA and then irradiated with {gamma}-IR: however reduced PTEN levels did not induce cell-cycle arrest or p21 expression. Conclusions: Taken together, these findings indicate that PTEN may modulate cell death or the cell cycle via AKT inactivation by PTEN and {gamma}-IR treatment. We also propose that a PTEN-PI3K/AKT-p21-CDK1 pathway could regulate cell death and the cell cycle by {gamma}-IR treatment.

• OSTI ID: 21124167
• Journal Information: International Journal of Radiation Oncology, Biology and Physics, Journal Name: International Journal of Radiation Oncology, Biology and Physics Journal Issue: 5 Vol. 70; ISSN IOBPD3; ISSN 0360-3016
• Country of Publication: United States
• Language: English

Related Subjects

62 RADIOLOGY AND NUCLEAR MEDICINE
APOPTOSIS
CARCINOMAS
CELL CYCLE
CHROMOSOMES
GAMMA RADIATION
LUNGS
MONOCLINIC LATTICES
MUTANTS
PHOSPHORYLATION
PLASMIDS
STEADY-STATE CONDITIONS