Functionalβ-adrenergic receptors in breast cancer cells

Abstract

Using L-[3H]dihydroalprenolol [( 3H]DHA), a potent beta-adrenergic antagonist, we demonstrated in breast cancer cells the presence of beta-adrenergic receptors with high affinity (Kd 1-9 nM) as shown by Scatchard analyses. Natural and synthetic agonists inhibited the [3H]DHA binding in the following order of potency: L-isoproterenol = L epinephrine much much greater L-norepinephrine, identical to the well-established order of potency for these compounds in producing beta-adrenergic responses. We verified that these compounds actually stimulated cAMP production in breast cancer cells. At the present time, the pathophysiological significance of beta-adrenergic receptors remains unclear. In view of the importance of cAMP in lactose production and in tumor growth mechanisms, it seems to be important to characterize the beta-adrenergic receptors in breast cancer cells in more detail and study their possible involvement in breast tumor growth.

Beta-Blocker Drug Therapy Reduces Secondary Cancer Formation in Breast Cancer and Improves Cancer Specific Survival

“…It has been shown that norepinephrine can directly stimulate tumour cell migration and this effect is mediated by the beta-adrenergic receptor, β2AR. High levels of β 2 AR have been reported in human cell lines [11,23,24] and tumour samples [25] and importantly, we have shown that cell migration in a number of cancer models is inhibited by the beta-blocker adrenergic receptor antagonist, propranolol [11,12,14].…”

Neuroendocrine influences on cancer biology

“…Depending on the tumor type, adrenergic receptor, and stress-related hormones, the effects of stress-related hormones on tumor cell proliferation can be either stimulatory or inhibitory. For example, in a breast cancer model, activation of beta-adrenergic receptors (ADRB) has been shown to accelerate tumor growth [19,20,26]. In contrast, Carie and Sebti have demonstrated that ADRB2 agonist pirbuterol causes human tumor regression in MDA-MB-231 breast cancer in vivo by blocking the Raf-1/Mek-1/Erk1/2 pathway.…”

“…However, the uncertain role of the immune system in regulating solid tumor growth led us to consider an alternative hypothesis: stress mediators from the sympathetic nervous system might directly regulate the growth and metastatic potential of tumor cells, independent of the effects on the immune system [17]. Recently, there is growing evidence confirming that alterations in neuroendocrine dynamics due to chronic stress can cause alterations in tumor pathogenesis [17][18][19][20][21]. In this review, we will focus on these biological pathways that may be affected by stress mediators.…”

The Neuroendocrine Impact of Chronic Stress on Cancer

“…For example, in breast carcinoma, activation of b-adrenergic receptors (ADRB) has been associated with accelerated tumor growth. [18][19][20] In contrast, catecholamines may inhibit tumor cell proliferation that may be mediated by a-adrenergic receptors or the dopamine transporter. Scarparo and colleagues found that melanoma cells treated with the a 1 -adrenergic agonist phenylephrine led to a dose-dependent decrease in proliferation, which could be reversed by the a 1 -adrenergic antagonist prazosin.…”