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Autocrine regulation of DU145 human prostate cancer cell growth by epidermal growth factor‐related polypeptides

1991; Wiley; Volume: 19; Issue: 2 Linguagem: Inglês

10.1002/pros.2990190210

1097-0045

Jeanne M. Connolly, David P. Rose,

Cell Adhesion Molecules Research

Abstract The DU145 human prostate cancer cell line possesses epidermal growth factor (EGF) receptors and synthesizes both EGF and the related polypeptide transforming growth factor α (TGF‐α). 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 [ 125 I]EGF for binding to DU145 cell binding sites over a 1 × 10 −11 to 1 × 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 × 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 × 10 −9 M antibody concentration. It is concluded that DU145 cell growth is regulated by an EGF‐mediated autocrine loop.