AUTOCRINE REGULATION OF DU145 HUMAN PROSTATE-CANCER CELL-GROWTH BY EPIDERMAL GROWTH FACTOR-RELATED POLYPEPTIDES

The DU145 human prostate cancer cell line possesses epidermal growth factor (EGF) receptors and synthesizes both EGF and the related polypeptide transforming growth factor-alpha (TGF-alpha). A monoclonal antibody to the EGF receptor was used to determine whether these characteristics were indicative of a functional autocrine regulatory system. This antibody competed effectively with [I-125]EGF for binding to DU145 cell binding sites over a 1 x 10(-11) to 1 x 10(-7) M concentration range, and did so with a capability similar to that of the two natural ligands. It inhibited growth of these cells in both 3% fetal bovine serum-supplemented and serum-free medium; in experiments with incubation times of 3-5 days there was a 45-50% reduction in cell number. Growth suppression by the EGF receptor blockade of cells plated at a density of 1.5 x 10(4) cells/ml/well was reversed competitively by the addition of EGF to the medium; 0.3 nM completely eliminated the inhibitory effect of a 1 x 10(-9) M antibody concentration. It is concluded that DU145 cell growth is regulated by an EGF-mediated autocrine loop.