Oxygen environment-dependent modulation of growth factor response in cancerous cells
Disciplines
Biochemistry | Biological Phenomena, Cell Phenomena, and Immunity | Cancer Biology | Cell Biology | Chemical and Pharmacologic Phenomena | Molecular Biology
Abstract (300 words maximum)
In homeostatic conditions, different tissues in the body require varying levels of available oxygen. However, in certain disease states – such as tumor hypoxia or ischemia/reperfusion injury – these oxygen levels can be altered. While some consequences of changes in oxygen levels are known, as in HIF1a-mediated intracellular responses to hypoxia, the effects of lesser changes on many cellular processes are yet to be identified. Here, we sought to understand the effect of differing oxygen levels on cellular responses to growth factor stimulation by culturing the human cancer cell lines MCF7 (invasive ductal carcinoma) and U2OS (osteosarcoma) in either 6% or 21% oxygen and stimulating them with epidermal growth factor (EGF). At set time points after stimulation, percent phosphorylation of extracellular signal-regulated kinase isoforms 1 and 2 (ERK 1 and 2), which function downstream of the EGF receptor, was measured via immunoblotting. In MCF7 cells, percent phosphorylation in 6% oxygen was shown to be distinctly higher than in 21% oxygen while in U2OS cells such a distinction was not seen, however there is a significant deviation in the percent phosphorylation values between separate time courses of the same cell type. Additionally, the phosphorylation of ERK 1 and 2 differed in both cell types and both oxygen environments. These data could suggest variations in oxygen environment-dependent outcomes of growth factor stimulation between epithelial tissue- and connective tissue-derived cancer cells and also may provide evidence of oxygen-dependent regulatory differences between ERK isoforms 1 and 2.
Academic department under which the project should be listed
CSM - Chemistry and Biochemistry
Primary Investigator (PI) Name
Carol Chrestensen
Oxygen environment-dependent modulation of growth factor response in cancerous cells
In homeostatic conditions, different tissues in the body require varying levels of available oxygen. However, in certain disease states – such as tumor hypoxia or ischemia/reperfusion injury – these oxygen levels can be altered. While some consequences of changes in oxygen levels are known, as in HIF1a-mediated intracellular responses to hypoxia, the effects of lesser changes on many cellular processes are yet to be identified. Here, we sought to understand the effect of differing oxygen levels on cellular responses to growth factor stimulation by culturing the human cancer cell lines MCF7 (invasive ductal carcinoma) and U2OS (osteosarcoma) in either 6% or 21% oxygen and stimulating them with epidermal growth factor (EGF). At set time points after stimulation, percent phosphorylation of extracellular signal-regulated kinase isoforms 1 and 2 (ERK 1 and 2), which function downstream of the EGF receptor, was measured via immunoblotting. In MCF7 cells, percent phosphorylation in 6% oxygen was shown to be distinctly higher than in 21% oxygen while in U2OS cells such a distinction was not seen, however there is a significant deviation in the percent phosphorylation values between separate time courses of the same cell type. Additionally, the phosphorylation of ERK 1 and 2 differed in both cell types and both oxygen environments. These data could suggest variations in oxygen environment-dependent outcomes of growth factor stimulation between epithelial tissue- and connective tissue-derived cancer cells and also may provide evidence of oxygen-dependent regulatory differences between ERK isoforms 1 and 2.