Human breast cancer cell line MDA‐MB‐231 expresses endogenous A2B adenosine receptors mediating a Ca2+ signal
M Panjehpour, M Castro… - British journal of …, 2005 - Wiley Online Library
M Panjehpour, M Castro, KN Klotz
British journal of pharmacology, 2005•Wiley Online Library1 Two human breast cancer cell lines, MCF‐7 and MDA‐MB‐231, were screened for the
presence of functionally significant adenosine receptor subtypes. 2 MCF‐7 cells did not
contain adenosine receptors as judged by the lack of an effect of nonselective agonists on
adenylyl cyclase activity or intracellular Ca2+ levels. MDA‐MB‐231 cells showed both a
stimulation of adenylyl cyclase and a PLC‐dependent increase in intracellular Ca2+ in
response to nonselective adenosine receptor agonists. 3 Both adenosine‐mediated …
presence of functionally significant adenosine receptor subtypes. 2 MCF‐7 cells did not
contain adenosine receptors as judged by the lack of an effect of nonselective agonists on
adenylyl cyclase activity or intracellular Ca2+ levels. MDA‐MB‐231 cells showed both a
stimulation of adenylyl cyclase and a PLC‐dependent increase in intracellular Ca2+ in
response to nonselective adenosine receptor agonists. 3 Both adenosine‐mediated …
- 1Two human breast cancer cell lines, MCF‐7 and MDA‐MB‐231, were screened for the presence of functionally significant adenosine receptor subtypes.
- 2MCF‐7 cells did not contain adenosine receptors as judged by the lack of an effect of nonselective agonists on adenylyl cyclase activity or intracellular Ca2+ levels. MDA‐MB‐231 cells showed both a stimulation of adenylyl cyclase and a PLC‐dependent increase in intracellular Ca2+ in response to nonselective adenosine receptor agonists.
- 3Both adenosine‐mediated responses in MDA‐MB‐231 cells were observed with the nonselective agonists 5′‐N‐ethylcarboxamidoadenosine (NECA) and 2‐(3‐hydroxy‐3‐phenyl)propyn‐1‐yladenosine‐5′‐N‐ethyluronamide (PHPNECA), but no responses were observed with agonists selective for A1, A2A or A3 adenosine receptors. The Ca2+ signal was antagonized by 8‐cyclopentyl‐1,3‐dipropylxanthine (DPCPX) and the nonselective antagonist 9‐ethyl‐8‐furyladenine (ANR 152), but not by A2A or A3 selective compounds.
- 4In radioligand binding with [2‐3H](4‐(2‐[7‐amino‐2‐(2‐furyl)[1,2,4]triazolo[2,3‐a][1,3,5]triazin‐5‐ylamino]ethyl)phenol) ([3H]ZM 241385), a specific binding site with a KD value of 87 nM and a Bmax value of 1600 fmol mg−1 membrane protein was identified in membranes from MDA‐MB‐231 cells.
- 5The pharmacological characteristics provide evidence for the expression of an A2B adenosine receptor in MDA‐MB‐231 cells, which not only mediates a stimulation of adenylyl cyclase but also couples to a PLC‐dependent Ca2+ signal, most likely via Gq/11. The A2B receptor in such cancer cells may serve as a target to control cell growth and proliferation.
- 6The selective expression of high levels of endogenous A2B receptors coupled to two signaling pathways make MDA‐MB‐231 cells a suitable model for this human adenosine receptor subtype.
British Journal of Pharmacology (2005) 145, 211–218. doi:10.1038/sj.bjp.0706180
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