Growth hormone binding to cultured human breast cancer cells.

The role of pituitary hormones in the pathogenesis of human breast cancer is unclear, although hypophysectomy is of therapeutic benefit in some patients with advanced breast cancer. Agents that lower serum PRL are of little value in the treatment of breast cancer, suggesting that other pituitary hormones may be important in the control of the growth of human breast cancer in vivo. Since human (h) GH is lactogenic in rodents, we investigated the binding of [125I]hGH and [125I]hPRL to the cultured human breast cancer cell lines T-47D and MCF-7. Both [125I]hGH and [125I]hPRL bound to a saturable binding site with high affinity (Ka = 0.94-1.70 X 10(9) M-1) and low capacity (4140-6560 sites/cells) in the two cell types. hGH and hPRL were mutually competitive, indicating that both hormones bound to the same receptor site. After binding of [125I]hGH to cell monolayers, the hormone was rapidly internalized in a time-, temperature-, and energy-dependent fashion. Lysosomotropic agents inhibited degradation of [125I]hGH and enhanced specific binding. Preincubation of MCF-7 cells with either hGH or hPRL resulted in loss of hGH/hPRL-binding sites, although hGH was consistently more potent in inducing down-regulation of the receptor. On the basis of these observations we suggest that hGH is a potent ligand for the lactogenic receptor in human breast cancer cells in vitro and may be important in the pathogenesis, growth, and metastasis of human breast cancer.