| Zdroj: |
Cancer Chemotherapy & Pharmacology; Jul2006, Vol. 58 Issue 1, p50-61, 12p, 1 Color Photograph, 1 Diagram, 2 Charts, 4 Graphs |
| Abstrakt: |
Adrenergic compounds (epinephrine and norepinephrine) are the most important hormones released during stress. Several different receptors are associated with their action in different tissues. However, α2-adrenoceptors have not yet been described in either normal or tumour human breast tissue. The aim of this work was to describe and characterize these receptors in several tumour and non-tumour human cell lines. The expression of α2-adrenoceptors was analyzed at the RNA (RT-PCR) and protein ([3H]-rauwolscine binding and immunocytochemistry) levels in different human breast cell lines, and the biological activity assessed by [3H]-thymidine incorporation. The cancer IBH-6, IBH-7 and MCF-7 and the non-tumour HBL-100 cells line, expressed both α2B- and α2C-adrenoceptor-subtypes. A single subtype was expressed in malignant HS-578T (α2A) and MDA-MB-231 and non-tumour MCF-10A cells (α2B). All cell lines exhibited significant binding for the specific antagonist [3H]-rauwolscine. The α-, α2-, and the α1-compounds with known affinity for α2-adrenoceptors, including epinephrine, norepinephrine, yohimbine, clonidine, rauwolscine and prazosin, competed significantly with binding in MCF-7 cells. In addition, IBH-6, IBH-7 and MCF-7 cells showed significant staining with specific antibodies against α2B- and α2C-adrenoceptor-subtypes, when tested by immunocytochemistry. In all cell lines, the specific agonist clonidine or oxymetazoline stimulated [3H]-thymidine incorporation. EC50 values were in the range of 20–50 fM for IBH-6, IBH-7, and HS-578T; 0.14 pM for MCF-7; 2–82 pM for HBL-100 and MCF-10A cells, and a biphasic behaviour with a maximum value at 38.0 pM, was observed for MDA-MB-231 cells. The specific α2-adrenergic antagonist rauwolscine always reversed this stimulation at 0.1 nM. In conclusion, this study describes for the first time, the presence of α2-adrenoceptors in human epithelial breast cell lines. Moreover, activation of these receptors was associated with an enhancement of cell proliferation. [ABSTRACT FROM AUTHOR] |
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