Gonadotropin-releasing hormone (GnRH)-binding sites in human breast cancer cell lines and inhibitory effects of GnRH antagonists.
GnRH-binding sites have previously been described in human breast tumors, and a GnRH agonist has been shown to inhibit growth of the MCF-7 human breast cancer cell line. We have investigated the presence of GnRH-binding sites in ZR-75-1, MDA-MB-231, Sk Br 3, MDA-MB-157, and MCF-7 human breast cancer cell lines and the effect of GnRH analogs on the incorporation of [3H]thymidine and 14C-labeled amino acids into DNA and protein. Specific GnRH-binding sites were present in membrane preparations of all five human breast carcinoma cell lines. Studies in three cell lines indicated low affinity (Kd, 1.6-3.0 X 10(-6) M) GnRH binding similar to that reported in human placenta and corpus luteum. In contrast, human pituitary GnRH receptors were of high affinity (Kd, 4.8 X 10(-9) M). Breast carcinoma cell GnRH-binding sites also differed from the pituitary receptor in their inability to discriminate between GnRH and superactive analogs. Binding of a [125I]GnRH analog to ZR-75-1 breast cancer cells and pituitary membranes was affected similarly by various cations. GnRH antagonists rapidly inhibited [3H]thymidine incorporation into DNA (within 3 hr), and this effect was reversible. GnRH antagonists also inhibited cell growth, but only after 6 days. GnRH agonists did not alter either thymidine incorporation or growth. The present observations of low affinity GnRH-binding sites in breast cancer cell lines and inhibitory effects of GnRH antagonists point to the possibility of an autocrine regulatory role of GnRH-like peptides in mammary cells.
D001943:Breast Neoplasms / Q000032:analysis*; D002064:Buserelin / Q000494:pharmacology; D002460:Cell Line; D004261:DNA Replication / Q000187:drug effects; D007987:Gonadotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006801:Humans; D010446:Peptide Fragments / Q000494:pharmacology; D011966:Receptors, LHRH / Q000032:analysis*; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology
D010446:Peptide Fragments; D011966:Receptors, LHRH; D007987:Gonadotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone; D002064:Buserelin