Biological effects of biosynthetic human EGF on the growth of mammalian cells in vitro.

The effects were examined of biosynthetic human epidermal growth factor (Bh-EGF) produced from cloned E. coli on DNA synthesis and all divisions of 13 different kinds of primary and established cell lines. Primary cultures of mammary epithelia, hepatocytes and stomach cells were strongly stimulated by EGF to undergo DNA synthesis in serum-free culture medium with concentrations of Bh-EGF as low as 0.1-10 ng/ml. In sharp contrast, 0.1-100 ng/ml of Bh-EGF failed to enhance thymidine incorporation into DNA when applied to established cell lines using the serum-free medium. Higher concentrations of Bh-EGF (30-100 ng/ml) promoted morphological changes only in hepatocytes, e.g., elongation, enlargement and projection of their cytoplasm. The above results were also obtained in mouse EGF (m-EGF). In our binding assay, Bh-EGF competed against [125I]-m-EGF with a one-fourth to one-fifth efficacy when compared with m-EGF. It was concluded that the in vitro biological activity of Bh-EGF was similar to that of m-EGF.