Receptors for d-Trp6-Luteinizing Hormone-Releasing Hormone, Somatostatin, and Insulin-Like Growth Factor I in MXT Mouse Mammary Carcinoma (42987)

Gordan Srkalovic, Bela Szende, Tommie W. Redding, Kate Groot, Andrew V. Schally

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Abstract

Membrane receptors for d-Trp6-luteinizing hormone-releasing hormone (d-Trp6-LH-RH), somatostatin-14 (SS-14), and insulin-like growth factor I (IGF-I) were estimated in MXT mammary cancers of mice using sensitive multipoint micromethods. The receptors were characterized in untreated animals and following in vivo treatment with microcapsules of the agonist d-Trp6-LH-RH and the somatostatin analog RC-160, which strongly inhibited tumor growth. In the control group, d-Trp6-LH-RH was bound to the single class of saturable, specific, noncooperative receptor sites (Kd, = 29.3 ± 8.48 × 10-9M; Bmax = 4.55 ± 0.31 pmol/mg membrane protein). Treatment with d-Trp6-LH-RH alone or in combination with RC-160 produced down-regulation of membrane receptors for d-Trp6-LH-RH on MXT mammary tumor cells. RC-160 alone and ovariectomy were without effect on d-Trp6-LH-RH receptors. On the membrane surface of MXT mammary cells, we found one class of high affinity, specific, saturable binding sites for SS-14 (Kd = 4.4 ± 1.9 × 10-9M; Bmax = 0.58 ± 0.21 pmol/mg membrane protein). Treatment with RC-160 alone or combined with d-Trp6-LH-RH significantly increased both the dissociation binding constant (Kd = 18.6 ± 3.5 × 10-9 and 10.1 ± 0.7 × 10-9M, respectively) and the binding capacity (Bmax = 13.98 ± 1.7 and 21.00 ± 4.0 pmol/mg membrane protein, respectively). We also found specific binding sites (Kd = 3.01 ± 0.15 × 10-9M; Bmax = 2.24 ± 0.96 pmol/mg membrane protein) for IGF-I in the membrane fractions of MXT mammary cancers. Chronic treatment with d-Trp6-LH-RH and RC-160 alone or in combination, as well as ovariectomy, significantly decreased the dissociation binding constant of IGF-I membrane receptors on MXT mammary cells. Our results strongly suggest an important role of LH-RH, SS-14, and IGF-I in the growth of MXT mammary carcinoma. Changes in characteristics of receptors after treatment with analogs of LH-RH and SS-14 along with tumor growth inhibition provide additional support for the direct effect of these peptides on tumor cells. A possible significance of these findings as applied to a clinical environment is discussed.

Original languageEnglish
Pages (from-to)209-218
Number of pages10
JournalProceedings of the Society for Experimental Biology and Medicine
Volume192
Issue number3
DOIs
Publication statusPublished - Dec 1989

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ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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