Direct effects of luteinizing hormone-releasing hormone agonists and antagonists on MCF-7 mammary cancer cells.
| dc.creator | Segal-Abramson, T | |
| dc.creator | Kitroser, H | |
| dc.creator | Levy, J | |
| dc.creator | Schally, A V | |
| dc.creator | Sharoni, Y | |
| dc.date | 1992-03-15 | |
| dc.date.accessioned | 2026-08-03T01:29:41Z | |
| dc.description | The binding of luteinizing hormone-releasing hormone (LH-RH) analogues to the human mammary tumor cell line MCF-7 and their effect on the cell proliferation was studied to elucidate their direct action on estrogen-dependent mammary tumors. The growth rate of these cells was doubled by the addition of 1 nM estradiol to cells maintained in an estrogen-deficient medium. Although the basal growth rate was only slightly inhibited by the LH-RH antagonist [Ac-D-Nal(2)1,D-Phe(pCl)2,D-Pal(3)3,D-Cit6,D-Ala10]LH-RH (SB-75), the estrogen-stimulated growth was completely abolished by the antagonist. In contrast, the LH-RH agonist buserelin stimulated cell growth in estrogen-deficient medium, whereas it had no effect in the presence of estrogen. 125I-labeled buserelin was used for the measurement of LH-RH receptors on MCF-7 cells. A Scatchard plot analysis of buserelin-specific binding revealed a nonlinear plot, which suggested the presence of one high-affinity binding site with a Kd of 1.4 +/- 1.0 nM and the remaining sites with low affinity (Kd = 1.3 +/- 1.0 microM). The binding of 125I-labeled buserelin was displaced equally well by unlabeled buserelin and by the LH-RH antagonist SB-75, suggesting that both analogues are bound to the same receptor. When parallel experiments were performed with 125I-labeled SB-75, the binding was displaced by unlabeled SB-75 and other antagonists, but only partially displaced by unlabeled buserelin. The results suggest that in these mammary tumor cells there is a LH-RH antagonist binding site that is not recognizable by LH-RH agonists. This hypothesis was tested by measuring cell growth in the presence of both agonists and antagonists. It was found that SB-75 inhibited the stimulation of growth by buserelin, but buserelin did not prevent the inhibition by the antagonist of the estrogen-dependent growth. These results suggest that antagonists directly inhibit mammary tumor growth, not only by competing with LH-RH high-affinity receptors, but also by other mechanisms mediated by low-affinity antagonist binding sites. IMAGES: | |
| dc.identifier | https://pmc.ncbi.nlm.nih.gov/articles/PMC48652/ | |
| dc.identifier | https://pubmed.ncbi.nlm.nih.gov/1312718/ | |
| dc.identifier | https://doi.org/10.1073/pnas.89.6.2336 | |
| dc.identifier.uri | https://repo.dare.co.zw/handle/123456789/154791 | |
| dc.language | en | |
| dc.publisher | National Academy of Sciences | |
| dc.source | Proc Natl Acad Sci U S A | |
| dc.subject | Research Article | |
| dc.title | Direct effects of luteinizing hormone-releasing hormone agonists and antagonists on MCF-7 mammary cancer cells. | |
| dc.type | Text |