Growth of human breast cancer cells inhibited by a luteinizing hormone-releasing hormone agonist

Abstract

About one-third of human breast cancers require hormones for their continued growth and endocrine ablation or anti-hormone therapy can cause regression of these tumours. As a consequence, ovariectomy in premenopausal women or administration of an anti-oestrogen (tamoxifen) in postmenopausal women represent major options for treatment of metastatic breast cancer. Alternatively, chronic administration of agonistic analogues of luteinizing hormone-releasing hormone (LHRH) causes regression of mammary tumours in experimental animals, and such treatment has shown promise in a small series of premenopausal women with advanced breast cancer. It has been assumed that these results were achieved by suppressing the pituitary-ovarian axis, as the treatment causes a reduction in circulating levels of gonadal steroids similar to that produced by castration. However, LHRH agonists can exert major effects on tissues other than the pituitary in animals and in the human. Such findings, coupled with reports of LHRH in human breast milk and immunohistochemical evidence for the presence of LHRH-like activity in some human breast tumours, prompted us to test whether LHRH agonists could have direct antitumour effects. We now report major direct effects of LHRH and its agonists on the growth of breast tumour cells in culture.

Diversity of actions of GnRHs mediated by ligand-induced selective signaling

“…The presence of GnRH receptors in breast cancer tissue [31] and the demonstration of antiproliferative actions of GnRH analogs in breast cancer cell lines [32,47,96] supported this interpretation. Antiproliferative effects of GnRH analogs and the expression of GnRH receptors have now been demonstrated in a number of cell lines of reproductive tract tumors, including prostate, uterine and ovarian cancers, and also in nonreproductive tract tumors [21,43,47,70,73,79].…”

The effects of gonadotrophin releasing hormone analogues in prostate cancer are mediated through specific tumour receptors

“…There have also been reports of the presence of GnRH-binding sites in breast cancer cells (Eidne et al, 1987), pancreatic tumours (Szende et al, 1989) and induced rat prostatic cancers (Kadar et al, 1988). The binding of GnRH to breast cancer cells has been shown to result in growth modulation (Millar et al, 1985;Eidne et al, 1987). The finding of specific GnRH-binding sites in prostatic cancer cells which modulate growth, and the observation of the secretion of GnRH-like peptides by these cells, suggests that GnRH-like peptides may play an autocrine stimulatory role in this system.…”

Expression of the gene for the receptor of gonadotropin‐releasing hormone in the rat mammary gland

“…In both reports, the extrapituitary GnRH receptor transcripts were found to have nucleotide sequence identical with that of the pituitary gland. Although GnRH analogs have been demonstrated to exhibit direct effects on growth rate of MCF-7 cells [3,4,24], the affinity and even the detection of specific binding sites for GnRH in this cell line is still a matter of controversy [21,22,24]. Heterogeneity of receptors has been recognized to be an efficient way for obtaining different biological responses to a single hormone stimulation.…”