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 [125I]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.
Connolly
J M
JM
Division of Nutrition and Endocrinology, Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York 10595.
Rose
D P
DP
D000911:Antibodies, Monoclonal; D001667:Binding, Competitive; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D004815:Epidermal Growth Factor / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D006801:Humans; D008297:Male; D011471:Prostatic Neoplasms / Q000473:pathology*; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D014407:Tumor Cells, Cultured
D000911:Antibodies, Monoclonal; D016211:Transforming Growth Factor alpha; D004815:Epidermal Growth Factor; D066246:ErbB Receptors