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

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

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)251-263
Number of pages13
JournalBreast Cancer Research and Treatment
Volume13
Issue number3
DOIs
Publication statusPublished - Oct 1989

Keywords

  • beta-adrenergic receptor
  • breast cancer
  • catecholamines
  • DMBA-induced rat mammary carcinoma
  • estrogen-sensitive cancer
  • progesterone receptor
  • spontaneous mammary tumors

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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