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 wi de variety of epithelial cells, including recently, dog thyroid follic ular cells. Here we have extended this work to human thyrocytes, and f ind that recombinant HGF stimulates DNA synthesis (proportion of cells in cell cycle S phase) in normal primary cells in monolayer, with an ED(50) of similar to 8 ng/ml and a maximum between 50 and 250 ng/ml. S timulation 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 H-3-thymidine labelling index achieved with HGF being up to 6-fold higher than that with serum alone. A similar additive eff ect was observed on thyrocytes already stimulated to proliferate by ex pression 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 advant age even in neoplastic thyroid cells, consistent with the finding of i ncreased met expression in many thyroid carcinomas.