Presence and characteristics of receptors for [D-Trp6]luteinizing hormone releasing hormone and epidermal growth factor in human ovarian cancer

Gordan Srkalovic, Andrew V Schally, James L. Wittliff, Thomas G. Day, Eric L. Jenison

Research output: Contribution to journalArticle

51 Citations (Scopus)

Abstract

This study was undertaken to establish the presence and characteristics of receptors for [D-Trp6]LH-RH on the membranes of human ovarian cancer. Specific binding of [125I, D-Trp6]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 noncooperative 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)=2.71±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-Trp6]LH-RH. Using 125I-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.

Original languageEnglish
Pages (from-to)489-498
Number of pages10
JournalInternational Journal of Oncology
Volume12
Issue number3
StatePublished - Mar 1 1998
Externally publishedYes

Fingerprint

Epidermal Growth Factor
Gonadotropin-Releasing Hormone
Ovarian Neoplasms
LH Receptors
Ovary
Membrane Proteins
Neoplasms
Membranes
Peptide Hormones
Therapeutic Uses
Somatostatin
Intercellular Signaling Peptides and Proteins
Binding Sites
Cell Membrane
Ligands
Carcinoma

Keywords

  • EGF receptors
  • LH-RH analogs
  • LH-RH receptors
  • Ovarian cancer

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Presence and characteristics of receptors for [D-Trp6]luteinizing hormone releasing hormone and epidermal growth factor in human ovarian cancer. / Srkalovic, Gordan; Schally, Andrew V; Wittliff, James L.; Day, Thomas G.; Jenison, Eric L.

In: International Journal of Oncology, Vol. 12, No. 3, 01.03.1998, p. 489-498.

Research output: Contribution to journalArticle

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abstract = "This study was undertaken to establish the presence and characteristics of receptors for [D-Trp6]LH-RH on the membranes of human ovarian cancer. Specific binding of [125I, D-Trp6]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 noncooperative 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)=2.71±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-Trp6]LH-RH. Using 125I-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.",
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