Veber N, Prévost G, Planchon P, Starzec A
Institut d'Oncologie Cellulaire et Moléculaire Humaine, IOCMH, Bobigny, France.
Eur J Cancer. 1994;30A(9):1352-9. doi: 10.1016/0959-8049(94)90186-4.
MDA-MB-231 is a breast epithelial cell line which possesses large amounts of epidermal growth factor (EGF) receptor on its cell surface but does not respond to EGF under standard culture conditions. 8-bromo-cyclic AMP (8Br-cAMP) and cholera-toxin treatments inhibit its growth by increasing its intracellular cAMP level. However, when inhibited in this way, MDA-MB-231 remains unresponsive to EGF. Similar effects--cAMP accumulation and inhibition of cell growth--are produced by forskolin. In addition, this substance specifically blocks MDA-MB-231 cells in G1 phase of the cell cycle. EGF is able to reverse the effect of forskolin on cell proliferation and prevents accumulation of cells in G1 phase without any change of cAMP level. Thus, only when inhibiting cell growth with forskolin does a mitogenic effect of EGF become evident. As cAMP 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-cAMP-mediated effect of forskolin must be considered to explain this effect. In contrast, the mitogenic effect of EGF on the NPM14T4/9 breast epithelial cell line does not change in the presence of forskolin.
MDA-MB-231是一种乳腺上皮细胞系，其细胞表面具有大量表皮生长因子（EGF）受体，但在标准培养条件下对EGF无反应。8-溴环磷酸腺苷（8Br-cAMP）和霍乱毒素处理通过提高其细胞内cAMP水平来抑制其生长。然而，以这种方式受到抑制时，MDA-MB-231对EGF仍然无反应。毛喉素也会产生类似的效果——cAMP积累和细胞生长抑制。此外，这种物质能特异性地将MDA-MB-231细胞阻滞在细胞周期的G1期。EGF能够逆转毛喉素对细胞增殖的作用，并防止细胞在G1期积累，而cAMP水平没有任何变化。因此，只有在用毛喉素抑制细胞生长时，EGF的促有丝分裂作用才会明显。由于这三种化合物都会使cAMP增加到相似的程度，但只有毛喉素的作用会被EGF拮抗，我们认为必须考虑毛喉素的非cAMP介导作用来解释这种效应。相比之下，在有毛喉素存在的情况下，EGF对NPM14T4/9乳腺上皮细胞系的促有丝分裂作用没有改变。
