Epidermal growth factor as an autocrine modulator of stress response in mammary epithelial cells

Mouse mammary epithelial cells (NMuMG line) were heat shocked at 42 degrees C for up to 2 h, with continuous culture at 37 degrees C used as controls. EGF mRNA expression, determined by Northern blot hybridization, was increased 4- to 5-fold in heat-shocked cells compared with controls. Heat shock also induced accumulation of EGF immunoreactive protein in both media and cell lysates of NMuMG cells. Oligonucleotides antisense to the EGF mRNA blocked the: accumulation of EGF protein, while sense controls were without effect. Antisense oligonucleotide concentrations that inhibited EGF production by NMuMG cells during heat shock dramatically reduced the ability of cells to survive heat shock, while sense oligonucleotide did not affect cell survival. The antisense oligonucleotide inhibition of cell survival was reversed by adding EGF during the heat shock period. Thus the production of EGF or EGF-like peptides during periods of cellular stress may be an important survival mechanism in mammary epithelium.