Open AccessThe A2B adenosine receptor in MDA-MB-231 breast cancer cells diminishes ERK1/2 phosphorylation by activation of MAPK-phosphatase-1
Author(s) -
Marthe Koussémou,
Kristina Lorenz,
KarlNorbert Klotz
Publication year - 2018
Publication title -
plos one
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.99
H-Index - 332
ISSN - 1932-6203
DOI - 10.1371/journal.pone.0202914
Subject(s) - adenosine , adenosine receptor , adenylyl cyclase , receptor , forskolin , phosphorylation , microbiology and biotechnology , adenosine a2b receptor , mapk/erk pathway , biology , signal transduction , estrogen receptor , stimulation , chemistry , agonist , endocrinology , medicine , cancer research , biochemistry , cancer , breast cancer
It was previously shown that the estrogen-receptor negative breast cancer cell line MBA-MD-231 expresses high levels of A 2B adenosine receptors as the sole adenosine receptor subtype. These receptors couple to both, stimulation of adenylyl cyclase and a Ca 2+ signal. In order to establish a potential role of A 2B adenosine receptors in tumor growth and development MAPK signaling was investigated in these breast cancer cells. Although it is known that A 2B adenosine receptors may stimulate MAPK it was found that in MBA-MD-231 cells ERK1/2 phosphorylation is reduced upon agonist-stimulation of A 2B adenosine receptors. This reduction is also triggered by forskolin, but abolished by the PKA inhibitor H89, suggesting an important role for the cAMP-PKA pathway. Likewise, a role for intracellular Ca 2+ was established as the Ca 2+ chelator 1,2-bis-(o-aminophenoxy)-ethane- N , N , N ’, N ’-tetraacetic acid, tetraacetoxymethyl ester (BAPTA-AM) abolished the reduction of ERK1/2 phosphorylation triggered by A 2B stimulation. It was shown that various pathways downstream from A 2B adenosine receptors resulted in a stimulation of MAPK phosphatase-1 (MKP-1) which dephosphorylates phospho ERK1/2, and thus plays a critical role in the regulation of the phosphorylation state of ERK1/2. The reduction of ERK1/2 phosphorylation mediated by A 2B adenosine receptors might provide an interesting approach for adjuvant treatment leading to reduced growth of certain tumors expressing the A 2B subtype.