Mitogenic stimulation of normal and oncogene-transformed human thyroid epithelial cells by hepatocyte growth factor

Hepatocyte growth factor (HGF) has been shown to be mitogenic for a wide variety of epithelial cells, including recently, dog thyroid follicular cells. Here we have extended this work to human thyrocytes, and find that recombinant HGF stimulates DNA synthesis (proportion of cells in cell cycle S phase) in normal primary cells in monolayer, with an ED50 of approximately 8 ng/ml and a maximum between 50 and 250 ng/ml. Stimulation was observed even in the presence of 10% fetal calf serum (previously the most potent mitogen for these cells in our hands), the maximum nuclear 3H-thymidine labelling index achieved with HGF being up to 6-fold higher than that with serum alone. A similar additive effect was observed on thyrocytes already stimulated to proliferate by expression of an activated ret oncogene. These results make HGF the most potent defined mitogen for human thyrocytes to date, and suggest that upregulated HGF/met signalling may confer a significant growth advantage even in neoplastic thyroid cells, consistent with the finding of increased met expression in many thyroid carcinomas.