Human breast cancer cell line MDA-MB-231 expresses endogenous A2B adenosine receptors mediating a Ca2+ signal
Human breast cancer cell line MDA-MB-231 expresses endogenous A2B adenosine receptors mediating a Ca2+ signal
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DOI：
10.1038/sj.bjp.0706180
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发表时间：
2005-05-01
影响因子：
7.3
通讯作者：
Klotz, KN
中科院分区：
文献类型：
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作者：
Panjehpour, M;Castro, M;Klotz, KN
1对两种人乳腺癌细胞系MCF-7和MDA-MB-231进行了功能上有意义的腺苷受体亚型的筛选。2由于缺乏非选择性激动剂对腺苷酸环化酶活性或细胞内钙离子水平的影响，MCF-7细胞不含腺苷受体。非选择性腺苷受体激动剂5‘-N-乙基羧胺腺苷(NECA)和2-(3-羟基-3-苯基)丙烯氨基-1-腺苷-5’-N-乙基尿酸酰胺(PHPNECA)均可引起细胞内钙离子浓度的升高，但对A(1)、A(2A)或A(3)腺苷受体激动剂均无反应。钙信号可被8-环戊基-1，3-二丙基黄嘌呤和非选择性拮抗剂9-乙基-8-呋喃腺嘌呤拮抗，但不能被A(2A)或A(3)选择性化合物4与[2-H-3](4-(2-[7-氨基-2-(2-呋喃)[1，2，4]三唑并[2，3-a][1，3，5]三氮-5-氨基]乙基)苯酚([H-3]ZM 241385)结合，在MDA-MB-231细胞膜上发现了一个K-D值为87 nM，B-max为1600 fmol mg(-1)的膜蛋白结合部位。5药理学特征为在MDA-MB-231细胞中表达A(2B)腺苷受体提供了证据，该受体不仅介导腺苷环化酶的刺激，而且与PLC依赖的钙信号偶联，很可能是通过G(Q/11)。这种癌细胞中的A(2B)受体可以作为控制细胞生长和增殖的靶点。6高水平的内源性A2B受体的选择性表达与两条信号通路相连，使MDA-MB-231细胞成为适合这一人类腺苷受体亚型的模型。
1 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 responses in MDA-MB-231 cells were observed with the nonselective agonists 5'-N-ethylcarboxamidoadenosine (NECA) and 2-(3-hydroxy-3-phenyl) propyn-1-yladenosine5'- N-ethyluronamide (PHPNECA), but no responses were observed with agonists selective for A(1), A(2A) or A(3) 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 A(2A) or A(3) selective compounds.4 In radioligand binding with [2-H-3](4-(2-[7-amino-2-(2-furyl)[1,2,4] triazolo[2,3-a][1,3,5] triazin-5-ylamino] ethyl) phenol) ([H-3]ZM 241385), a specific binding site with a K-D value of 87 nM and a B-max value of 1600 fmol mg(-1) membrane protein was identified in membranes from MDA-MB-231 cells.5 The pharmacological characteristics provide evidence for the expression of an A(2B) 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 G(q/11). The A(2B) receptor in such cancer cells may serve as a target to control cell growth and proliferation.6 The 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.