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  • Title: Characterization of bombesin/gastrin-releasing peptide receptors in human breast cancer and their relationship to steroid receptor expression.
    Author: Halmos G, Wittliff JL, Schally AV.
    Journal: Cancer Res; 1995 Jan 15; 55(2):280-7. PubMed ID: 7812958.
    Abstract:
    Bombesin (BN) and its mammalian counterpart, gastrin-releasing peptide (GRP), are hormonally active peptides which appear to function as autocrine or paracrine growth factors in a variety of cells. As part of a long-term investigation of the relationship of peptide and steroid hormone receptors to breast cancer progression and treatment, we examined the binding of [125I-Tyr4]BN to membranes isolated from 100 human breast carcinomas. Thirty-three of these tumors expressed BN/GRP receptor levels of > 10 fmol/mg membrane protein. Two classes of [Tyr4]BN-binding sites were detected using Scatchard analyses of radioligand association data from hormone displacement curves. The high-affinity binding sites exhibited a mean dissociation constant (Kd1) of 2.1 nM and a mean specific binding capacity (Bmax1) of 237 fmol/mg membrane protein. The low affinity binding sites had a mean dissociation constant (Kd2) of 0.3 microM and a mean binding capacity (Bmax2) of 5.9 pmol/mg membrane protein. BN/GRP receptor expression in a breast carcinoma was unrelated to patient age. When the levels of BN/GRP receptors were compared to the content of the sex steroid receptors, a highly significant positive correlation (P < 0.005) was observed between the binding capacities of high-affinity [Tyr4]BN-binding sites and estrogen receptor levels and between the concentrations of low affinity [Tyr4]BN-binding sites and progestin receptor levels (P < 0.05). This represents the first report of these labile, regulatory proteins in biopsies of human breast carcinomas. Expression of specific receptor proteins for BN/GRP, potent mitogens, in a large number of human breast cancers suggests that they may be involved in tumor cell progression. The approach based on determination of BN/GRP receptors might be useful to guide a hormonal therapy with BN/GRP antagonists in some women with breast cancer.
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