GROWTH-INHIBITORY ACTIONS OF ANALOGS OF LUTEINIZING-HORMONE-RELEASINGHORMONE ON TUMOR-CELLS

The expression of LHRH and its receptor has been demonstrated in a num ber of human malignant tumors, including cancers of the breast, ovary, endometrium, and prostate. These findings suggest the presence of an autocrine regulatory system based on LHRH. Dose-dependent antiprolifer ative effects of LHRH agonists in cell lines derived from these cancer s have been observed by various investigators. LHRH antagonists also h ave marked antiproliferative activity in most of the ovarian, breast, and endometrial cancer cell lines tested. indicating that the dichotom y of LHRH agonists and antagonists might not apply to the LHRH system in cancer cells. Findings from our laboratories suggests that the clas sical LHRH receptor signal-transduction mechanisms, known to operate i n the pituitary, are not involved in the mediation of antiproliferativ e effects of LHRH analogues in cancer cells. Results obtained by sever al groups, including ours, instead suggest that LHRH analogies interfe re with the mitogenic signal transduction of growth-factor receptors a nd related oncogene products associated with tyrosine kinase activity. The pharmacological exploitation of these direct antiproliferative ac tions of LHRH analogues might provide new therapeutic approaches to th ese cancers. (C) 1997, Elsevier Science Inc.