Presence and characteristics of receptors for D-Trp(6) luteinizing hormone releasing hormone and epidermal growth factor in human ovarian cancer
Title
Presence and characteristics of receptors for D-Trp(6) luteinizing hormone releasing hormone and epidermal growth factor in human ovarian cancer
Creator
Srkalovic G; Schally A V; Wittliff J L; Day T G; Jenison E L
Publisher
International Journal of Oncology
Date
1998
1998-03
Description
This study was undertaken to establish the presence and characteristics of receptors for [D-Trp(6)]LH-RH on the membranes of human ovarian cancer. Specific binding of [I-125, D-Trp(6)]LH-RH was found in 29 of 37 (78.4%) ovarian cancers and in 6 of 11 (54.5%) non-malignant human ovaries. Ligand binding was dependent on time and plasma membrane concentration in a fashion expected of a peptide hormone. Saturation, kinetic and displacement data were consistent with the presence of a highly specific, single class of non-cooperative binding site. On the basis of receptors affinity, LH-RH-receptor-positive ovarian cancers could be divided into two groups: high affinity group (K-d=2.7+/-0.60 nM; B-max=0.46+/-0.07 pmol/mg membrane protein) comprising 55% of tumors, and low affinity group (K-d=78.0+/-19.6 nM; B-max=9.44+/-2.68 pmol/mg membrane protein) which included 45% of tumors. LH-RH antagonist Cetrorelix showed an affinity to LH-RH receptors on ovarian cancers 14 times higher than the agonist [D-Trp(6)]LH-RH. Using I-125-epidermal growth factor, specific high affinity receptors were also detected in membranes from 13 of 24 (54%) ovarian cancers and 5 of 11 (45%) non-malignant ovaries. The demonstration of LH-RH receptors in human ovarian cancers provides a rationale for the use of therapeutic approaches based on LH-RH analogues in this malignancy. The probable involvement of growth factors in the development of ovarian cancers suggests the merit of trying a combined therapy based on analogs of LH-RH and somatostatin for this carcinoma.
Subject
analogs; antagonists; binding-sites; chemotherapy; EGF receptors; estrogen; expression; gnrh; human endometrial carcinoma; LH-RH analogs; LH-RH receptors; Oncology; ovarian-cancer; rat; somatostatin
Identifier
n/a
Format
Journal Article
URL Address
n/a
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Rights
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Pages
489-498
Issue
3
Volume
12
Citation
Srkalovic G; Schally A V; Wittliff J L; Day T G; Jenison E L, “Presence and characteristics of receptors for D-Trp(6) luteinizing hormone releasing hormone and epidermal growth factor in human ovarian cancer,” NEOMED Bibliography Database, accessed May 10, 2024, https://neomed.omeka.net/items/show/8074.