PARENT SESSION

RRS-ASTRO Minisymposium on Radiation-Induced Signaling

(MS028) NF-kappaB Mediated Signaling Network in the Radioresistance of Human Breast Cancer Cells.

Semenenko, Vladimir^*,1, Dong, Shaozhong¹, Fan, Ming¹, Ahmed, Kazi¹, Li, Jian Jian ¹, ¹ Divisioin of Moledcular Radiobiology, West Lafayette, Indiana, USA

ABSTRACT- Recent cell culture results suggest that stress transcription factor NF-kappaB is a key gene regulator in ionizing radiation induced adaptive resistance tested in human breast cancer MCF-7, human and mouse skin epithelial cells, and human prostate cancer cells. NF-kappaB is found to be required for the radioresistance induced by overexpressing breast cancer gene Her-2. DNA microarray study demonstrates that a group of genes encoding signaling proteins appear to be associated with a temporal radioresistance in cells exposed to signal or multiple doses of ionizing radiation. In agreement with microarray data, protein levels of 14-3-3zeta, Cyclin B1, and GADD45beta are increased in the radioresistant MCF-7 population. In addition, NF-kappaB subunit p65 and phosphorylated ERK were found to be regulated oppositely in the radiation derived radioresistant population. Direct protein interaction between p65 and ERK was visualized in living cells by co-transfection of fluorescence-fusion vectors. Overall, these results demonstrate a possibility that NF-kappaB subunit p65 is able to interact with ERK to form a network for radiation induced adaptive response. NF-kappaB, ERK and GADD45beta may coordinate to increase cancer cell survival against the cytotoxicity induced by ionizing radiation.

Key words: Breast cancer cells, Radioresistance, Signal transduction, NF-kappaB