EVIDENCE FOR A GROWTH EFFECT OF EPIDERMAL GROWTH-FACTOR ON MDA-MB-231BREAST-CANCER CELLS

MDA-MB-231 is a breast epithelial cell line which possesses large amou nts of epidermal growth factor (EGF) receptor on its cell surface but does not respond to EGF under standard culture conditions. 8-bromo-cyc lic AMP (8Br-cAMP) and cholera-toxin treatments inhibit its growth by increasing its intracellular cAMP level. However, when inhibited in th is way, MDA-MB-231 remains unresponsive to EGF. Similar effects-cAMP a ccumulation and inhibition of cell growth-are produced by forskolin. I n addition, this substance specifically blocks MDA-MB-231 cells in G1 phase of the cell cycle. EGF is able to reverse the effect of forskoli n on cell proliferation and prevents accumulation of cells in G1 phase without any change of cAMP level. Thus, only when inhibiting cell gro wth with forskolin does a mitogenic effect of EGF become evident. As c AMP is increased to a similar degree by all three compounds, yet only the effect of forskolin is antagonised by EGF, we suggest that a non-c AMP-mediated effect of forskolin must be considered to explain this ef fect. In contrast, the mitogenic effect of EGF on the NPM14T4/9 breast epithelial cell line does not change in the presence of forskolin.