1 research outputs found
Irradiation of Epithelial Carcinoma Cells Upregulates Calcium-Binding Proteins That Promote Survival under Hypoxic Conditions
Hypoxia is thought to promote tumor
radio-resistance via effects
on gene expression in cancer cells that modulate their metabolism,
proliferation, and DNA repair pathways to enhance survival. Here we
demonstrate for the first time that under hypoxic condition A431 epithelial
carcinoma cells exhibit increased viability when exposed to low-dose
γ-irradiation, indicating that radiotherapy can promote tumor
cell survival when oxygen supply is limited. When assessed using iTRAQ
quantitative proteomics and Western blotting, irradiated tumor cells
were observed to significantly up-regulate the expression of calcium-binding
proteins CALM1, CALU, and RCN1, suggesting important roles for these
mediators in promoting tumor cell survival during hypoxia. Accordingly,
shRNA-knockdown of CALM1, CALU, and RCN1 expression reduced hypoxic
tumor cell resistance to low-dose radiation and increased apoptosis.
These data indicate that γ-irradiation of hypoxic tumor cells
induces up-regulation of calcium-binding proteins that promote cancer
cell survival and may limit the efficacy of radiotherapy in the clinic