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Characterization of Bombesin/Gastrin-releasing Peptide Receptors in Human Breast Cancer and Their Relationship to Steroid Receptor Expression¹

Endocrine, Polypeptide and Cancer Institute, Veterans Affairs Medical Center, New Orleans, Louisiana 70146, and Section of Experimental Medicine, Department of Medicine, Department of Medicine, Tulane University Medical School, New Orleans, Louisiana 70112 [G. H., A. V. S.]; and Hormone Receptor Laboratory, James Graham Brown Cancer Center, University of Louisville, Louisville, Kentucky 40292 [J. L. W.]

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 (K_d1) of 2.1 nM and a mean specific binding capacity (B_max1) of 237 fmol/mg membrane protein. The low affinity binding sites had a mean dissociation constant (K_d2) of 0.3 µM and a mean binding capacity (B_max2) 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.

¹ This work was supported by NIH Grant CA 40003 and the Medical Research Services of the Veterans Affairs Medical Center (to A. V. S.) and by a Phi Beta Psi Sorority grant to J. L. W. The contents of this paper are solely the responsibility of the authors and do not necessarily represent the official view of the National Cancer Institute.

² To whom requests for reprints should be addressed, at Veterans Affairs Medical Center, 1601 Perdido Street, New Orleans, LA 70146.

Received 6/10/94. Accepted 11/11/94.

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