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Beta-adrenergic receptors in DMBA-induced rat mammary tumors: Correlation with progesterone receptor and tumor growth

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In order to gain further knowledge about the potential role of catecholamines in mammary carcinoma, we have used the potent β-adrenergic antagonist cyanopindolol (CYP) as iodinated ligand to characterize β-adrenergic receptors in membranes prepared from mammary tumors induced by dimethylbenz(a)anthraene (DMBA) administration in the rat. The binding of [125I]CYP to membrane preparations of DMBA-induced rat mammary tumors is rapid at room temperature, reaching half maximal specific binding at 30 min of incubation. Scatchard analysis of the data indicates that [125I]CYP binds to a single class of high affinity sites (114 ± 2.1 fmoles/mg protein) at an apparent KD value of 38.0 ± 0.3 pM. The order of potency of a series of agonists to compete for [125I]CYP binding is consistent with interaction with a β2-subtype receptor: zinterol > (−)isoproterenol > (−)epinephrine» (−)norepinephrine. In addition, the potency of a series of specific β1, and β2 synthetic compounds to displace [125I]CYP in mammary tumors is similar to their potency in typical β2-adrenergic tissues. The binding of [125I]CYP to DMBA-induced rat mammary tumors shows a marked stereoselectivity, the (−)isomers of isoproterenol and propranolol being 150 and 80 times more potent, respectively, than their respective enantiomers. The autoradiographic localization of [125I]CYP performed on frozen sections revealed the presence of specific β-adrenergic receptors in all the malignant cells. Spontaneous mammary tumors of aging (18–22 months) female rats have high levels of β-adrenergic receptors. Castration decreased the concentration of [125I]CYP binding sites in DMBA-induced mammary tumors. A close correlation was observed between progressing, static, and regressing tumors after ovariectomy and β-adrenergic receptor concentration. The presence of β-adrenergic receptors in mammary tumors as well as the modulation of their level by ovarian hormones provides a mechanism for catecholaminergic influence in mammary cancer tissue.

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Author notes

  1. Bianca Marchetti

    Present address: Department of Pharmacology, Faculty of Medicine, University of Catania, 95125, Catania, Italy

Authors and Affiliations

  1. MRC Group in Molecular Endocrinology, Laval University Medical Center, 2705, Laurier Boulevard, G1V 4G2, Quebec, Canada

    Bianca Marchetti, Paulo G. Spinola, Martin Plante, Patrick Poyet, Nicole Folléa, Georges Pelletier & Fernand Labrie

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  1. Bianca Marchetti
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  2. Paulo G. Spinola
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Marchetti, B., Spinola, P.G., Plante, M. et al. Beta-adrenergic receptors in DMBA-induced rat mammary tumors: Correlation with progesterone receptor and tumor growth. Breast Cancer Res Tr 13, 251–263 (1989). https://doi.org/10.1007/BF02106575

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